Guest Editorial A n apparent a nom aly is that a m edical curriculum can b e considered com p lete even if it pays only passing reference to the largest organ in the human body, skele­ tal m uscle which can com prise up to 25 kg in the aver­ a g e male. Skeletal m uscle, it would seem , lacks the rom antic charism a o f that far m o re puny (less than 5 0 0 g) organ, the heart. Yet the established, indeed re­ vered specialities o f cardiology and cardiac surgery and a thriving industry in cardiovascular m edicin es attest to the far greater im portance hum ans and the m edical profession attach to their hearts. Physiotherapists, neu­ rologists and specialists in physical m ed icin e are perhaps the sole m edical practitioners for w h om dis­ orders o f skeletal m uscles are o f m o re than passing in­ terest. But if much o f m ed icin e has yet to em brace the sig­ nificance o f such a w eigh ty organ, powerful forces at its fringes will ultim ately influence that indifference. In­ d eed the sin gle m ost im portant factor in fluencing the Cinderella status o f skeletal m uscle in the m edical cur­ riculum has been the growth o f the exercise sciences. It is perhaps obvious that those w ho would study the human in m otion should begin to cham pion the study o f the organ o f m ovem ent. But even am ongst the exercise scientists there are still those w ho are reluctant to believe the im portance o f the skeletal muscles in exercise and sport. S o a popu­ lar view is that exercise perform ance esp ecially during high intensity exercise o f short duration is lim ited by the capacity o f the heart to provide an adequate o xy­ gen supply to the large m uscle mass that is activated during this type o f exercise. If this is true, the main e f­ fect o f physical training we are led to believe must be to develop so-called “cardiovascular fitness” . Yet there are solid argum ents that question the scientific validi­ ty o f the pioneerin g studies on which this concept is based.1 Furtherm ore the factor that best identifies success­ ful endurance athletes is the ability specifically o f their skeletal muscle to resist the developm ent o f fatigue dur­ ing p rolon g ed exercise.2 In these athletes it is their muscles, not their hearts, that determ in e their success. Then perhaps m ost challenging is the new paradigm which su ggests that the exercise tolerance o f persons with advanced heart disease is lim ited by an associat­ ed m yopathy (o f chronic disease), rather than by the severely im paired function o f their diseased hearts.3 A s a result, exercise training which im proves skeletal m uscle function, can enhance exercise capacity and re­ duce exercise-related sym ptom s even in persons with advanced heart disease, even heart failure.4 With such advances it is perhaps appropriate that the review section o f the first issue o f our re-launched Jour­ nal should focus attention on skeletal m uscle and e x ­ ercise. T h e aim has been to review various aspects o f skeletal m uscle function that will be o f interest to the different disciplines that com prise the m em bership o f the South African Sports M ed icine Association. In the article devoted to the basic sciences, Dr Kathryn Myburgh PhD, w ho has recently com pleted her post-doctoral studies in the m uscle research laborato­ ry o f Dr R oger Cooke in San Francisco, carefully reviews the historical developm ent, still less than 50 years old, o f the b iochem ical and structural studies that have laid the foundation o f the m odern understanding o f how m uscles contract. S he next discusses the different con­ tractile properties including force production and resis­ tance to fatigue o f the separate m uscle fibres and ex­ plains how the different (iso)form s o f the contractile pro­ teins can explain s o m e o f these functional differen ces She concludes that training and other interventions alter not on ly m uscle fibre size, their m itochondrial en­ zym e content and their substrate utilization patterns but also the m ix o f the different contractile protein isoforms com prising the different fibres. S h e wonders whether sporting success m ight b e linked to specific m olecular com binations in the different skeletal m uscle fibres. In­ d eed on e must ask whether one sp ecific com bination o f skeletal m uscle contractile protein isoforms explains the success o f the sprinters o f West African origin and another, different com bination the exceptional fatigue resistance o f the East African distance runners? C lear­ ly if we are to honour our continent and its peoples, those questions must b e tackled and answered by A fri­ can scientists. Perhaps Dr Myburgh’s article will have served its purpose if it were to encourage o n e young scientist to ch ose a career that will address these ques­ tions. T h e dynam ic disorders o f skeletal muscle provide an intriguing insight into the interface between the basic and the clinical sciences. Th ese extrem ely rare condi­ tions which produce sym ptom s only during exercise are o f interest to clinicians who must consider them in the differential diagnosis o f conditions causing exercise- related sym ptom s. For the basic scientist, patients with these conditions provide a unique m odel for the study o f the biochem ical changes causing (prem ature) fatigue during exercise. T h e surprising finding is that fatigue in patients with M cA rdle’s syndrom e occurs, as expect­ ed, without changes in blood lactate levels or blood pH but, m ore interestingly, without a large reduction in m uscle A T P concentrations SA JOURNAL OF SPORTS MEDICINE SEPTEMBER 1994 1 R ep ro du ce d by S ab in et G at ew ay u nd er li ce nc e gr an te d by th e P ub lis he r (d at ed 2 01 2. ) G U E S T EDITORIAL O n e explanation for this finding is that skeletal mus­ cle function during exercise is regulated to prevent a reduction in m uscle A T P content sufficiently large to produce m uscle rigor. This postulate holds that under any condition in which the rate o f m uscle A T P produc­ tion is approaching so m e m axim u m value, the rate o f muscle A T P use is reduced by regulatory processes that reduce the force and frequency o f m uscle fibre contrac­ tion (thereby reducing the rate o f ATP use). Thus in this model, fatigue o f skeletal muscle during exercise is con­ ceived as a regulatory process which links skeletal mus­ cle contractile function to the rate o f A TP production (perhaps through changes in the levels o f m etabolites o f A TP breakdown including Pi and A D P ) specifically to prevent the d evelop m en t o f m uscle rigor. A n other interesting finding is that patients with Mc- A rd le’s syndrom e exhibit an excessive rise in cardiac output, m uscle b lo od flow and ventilation during exer­ cise. This is because o f a large fall in peripheral vascu­ lar resistance caused by excessive vasodilation in the active skeletal muscles. M etabolic interventions that reduce m uscle A D P and Pi concentrations during exer­ cise reduce the vasodilation, the skeletal m uscle blood flow and ventilation. Interestingly the m etabolic disord­ er c o m m on to all form s o f m uscle disease is that mus­ cle A D P and Pi levels rise m ore rapidly than normal during exercise; conversely highly trained muscle is able to resist this change until very high intensities o f exer­ cise are reached. Hence these studies provide intriguing evidence for m etabolic factors in skeletal m uscle that influence the cardiovascular and respiratory response to exercise and the onset o f subjective sym ptom s o f fatigue. In the section dealin g with clinical aspects o f skele­ tal muscle, Dr M ike Lam bert and Professor Steven Den­ nis review perhaps the m ost co m m on skeletal muscle ailm ent in the exercising population, what is popular called m uscle stiffness but w hich now enjoys the m ore elaborate official title o f D elayed O nset M uscle S ore­ ness (DOM S). In this review we learn that D O M S is not due to lac­ tate accum ulation and retention in the previously ac­ tive muscles. This is perhaps on e o f the com m on est m isconception in the general sporting population. Rather D O M S is due to tissue d am age from which there is a delayed recovery; dam age is especially likely after eccentric exercise, a finding well-known to runners in the “down” Com rades Marathon. Each step on the long downhill section from K lo o f to the finish in Durban places a large eccentric load on the runner’s quadriceps muscles. A n d the results are very apparent the follow ­ ing day. Readers o f this article will now b e able to give a detailed scientific explanation to help their runners through their post-race misery. Practical inform ation provided by these authros is that neither anti-inflam m atory m edications nor rest m ake any real difference to the rate o f recovery from DOMS. But training reduces the amount o f muscle stiff­ ness sym ptom s during a subsequent bout o f similar e x­ ercise. Th is effect m ay last for w eeks to months. T h e wish o f the authors is that we have been able to convey som e o f the excitem ent and enthusiasm we feel in our studies o f skeletal m uscle in active persons and the relevance that such studies have for the exer­ cise sciences and for clinical sports m edicine. Lastly we would h op e that, perhaps, we have been able to convince you that, in exercise and sport, the heart o f the m atter is skeletal msucle. REFERENCES 1. Noakes TD. Implications o f exercise for prediction o f athletic per­ formance: A contemporary perspective. M ed Sci Sports Exerc 20: 319-330, 1988. 2. Coetzer P, Noakes TD, Sanders B, Lambert Ml, Bosch Afi, Wig­ gins T and Dennis SC. Superior fatigue resistance of elite black South African distance runners. J Appl Physiol 75: 1822-1827, 1993. 3. Minotti JR, Christoph I, Oka R, Weiner MW, Wells L and Massie BM. Impaired skeletal muscle function in patients with congestive heart failure. Relationship to systemic exercise performance. J Clin Inuest 88: 2077-2082, 1991. 4. Sulliuan MJ, Higginbotham M B and Cobb FR. Exercise training in patients with severe left uentricular dysfunction. Circulation 78: 506-515, 1988. Professor TIM NOAKES Guest Editor 2 SA JOURNAL OF SPORTS MEDICINE SEPTEMBER 1994 R ep ro du ce d by S ab in et G at ew ay u nd er li ce nc e gr an te d by th e P ub lis he r (d at ed 2 01 2. ) THE SOUTH AFRICAN JOURNAL OF SPORTS MEDICINE Guest Editor Prof T D Noakes University of Cape Town Editorial Board Dr M P Schwellrtus University of Cape Town Dr M E Moolla Private Practitioner Durban Dr A Venter Private Practitioner Bloemfontein Dr P de Jager Private Practitioner Pretoria Dr J Skouuno Private Practitioner Johannesburg Dr I Surve Private Practitioner Cape Town Dr P Schwartz Private Practitioner Port Elizabeth Prof G Strydom Potchefstroom University Prof R Stretch University of Fort Hare Mrs J Morton Private Physiotherapist Durban Mr D Rehbock Podiatrist Johannesburg International Advisory Board Lyle J Micheli Associate Clinical Professor of Orthopaedic Surgery Boston, USA Chester R Kyle Research Director, Sports Equipment Research Associates California, USA Prof HC Wildor Hollmann President des Deutschen SportSrztebundes Koln, West Germany Howard J Green Professor, Department of Kinesiology Ontario, Canada George A Brooks Professor, Department of Physical Education California, USA Neil F Gordon Director, Exercise Physiology Texas, USA Edmund R Burke Associate Professor, Biology D e p a rtm e n t, University of Colorado Colorado, USA Graham N Smith Physiologist Glasgow, Scotland VOLUM E 1 NUM BER 1 SEPTEMBER 1994 CONTENTS Editorial TD Noakes 1 Forthcoming Conferences 5 The Dynamic Disorders of Skeletal Muscle Metabolism with Special Reference to exercise TD Noakes 6 Muscle Proteins and the Contractile Properties of Muscle Fibres KH Myburgh 11 Delayed — Onset — Muscle — Soreness Ml Lambert and SC Dennis 18 Advances in Sports Equipment Technology that enhance performance CR Kyle 21 Die Effek van ’n Stresweerbaarheidsprogram op Valskermspringers D Scheepers en J Potgieter 30 THE EDITOR THE SOOTH AFRICAN JOURNAL OF SPORTS MEDICINE P O Box 38567, Pinelands 7430 PROD UCTION ADVERTISING Andrew T hom as Marika de Waal/Andrew Thom as PUB LISH ING R EPROD UCTION Qlenbarr Publishers cc Output Reproduction Dunkeld 2196 PRINTING Tel: (011) 442-9759 Hortors Fax: ( O i l ) 880-7898 Cover sponsored by Ciba-Geigy T h e view s expressed in individual articles are the personal view s o f the Authors and are not necessarily shared by the Editors, the Advertisers or the Publishers. 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Focus will b e on diseases o f over and undernutrition and life­ style, the role o f nutrition in PHC, nutritions and food policy, the sensory aspects o f fo o d and how it relates to the practice o f nutrition and dietetics and the food industry, nutrition education and sports nutrition. For further details please contact: M s Carol Herbert; Con­ gress Co-ordinating Com m ittee, P O Box 1209, Durban, 4000. Fax: (031) 304-9652. August, 1994. 40TH S A O A A N N U A L CONGRESS, PRETORIA. Guest speakers: Dr Allan E Gross, Toronto, Canada; Dr R W Bucholz, University o f Texas, USA. Con­ tact: Dr L van Wyk, 404 M u elm ed M edical Centre, 577 Pretorius Street, Arcadia, Pretoria, 0083. Tel: (012) 341-7573. O ctob er 3-4, 1994. W O R K S H O P O N COM PUTER- B A S E D E X E RC ISE FO R T E A C H IN G PHYSIOLOGY, A N D : O cto b er 5-7, 1994. 2 2 N D A N N U A L C O N G R E SS O N T H E PH Y SIO LO G IC A L S O C IE T Y O F S O U T H E R N A F R IC A , STE LLE N B O S C H . For further details please contact: Dr A W van Rijswijk, D epartm ent o f Human and A n im al Physiology, University o f Stellenbosch, 7600. O ctob er 5-7, 1994. SC IE N TIFIC C O N G R E S S O F SO UTH A F R IC A N A S S O C IA T IO N FOR LAB O R A TO R Y A N IM A L S C IE N C E (S A A L A S ), JO H AN N E SB U R G . T h e Transnet Conference Centre, Esselen Park near Jan Sm uts Airport. Contact: Miss M oniqu e d e Villiers, N a ­ tional Institute for Virology, Private B ag X4, S andring­ ham, 2131. Tel: (011) 882-9910. Fax (011) 882-0596. N o vem b er 27-30, 1994. T H E S O U T H E R N A F R IC A C A R D IA C S O C IE T Y 19TH B IE N N IA L CONGRESS. Education Building, University o f C ape Town. Contact: Mrs S ally Elliott, Postgraduate M edical Centre, U C T M ed School, Observatory, 7925. Tel: (021) 406-6381. Fax: (021) 448-6263. March 22-24, 1995. SIXTH SO UTH A F R IC A N SPO RTS M ED ICINE A S S O C IA T IO N CONGRESS, ELANGEN1 H O T E L DURBAN. Contact Mrs Miriam Tennant, Sports Medicine, U C T M edical School, Observatory, 7925. Tel: (021) 406-6504. Fax: (021) 47-7669. INTERNATIONAL August 10-14, 1994. C O M M O N W E ALTH G A M E S 1994, IN T E R N A T IO N A L SC IE N TIFIC CONGRESS, U N IV E R ­ SITY O F VICTORIA, BC, C A N A D A . Contact: C om m on ­ wealth G am es International S cien ce Congress, Confer­ ence Services, Division o f University Extension, Univer­ sity o f Victoria, P O Box 3030, Victoria BC, Canada V8W 3N6. Fax: 604 721 8774. August 17-19, 1994. 7TH IN T E R N A T IO N A L C O N ­ G RESS O N O B E SITY — S A T E LLIT E SYM POSIUM , QUEBEC, C A N A D A . Contact Exercise and O besity Sat­ ellite, c/-Angelo Tremblay, Physical Activity Sciences La­ boratory, PEPS, University Laval, Ste-Foy, Quebec, Cana­ da G1K 7P4. Tel: 418 656 7294. Fax: 418 656 3020. August 29-03 Sept, 1994. T H E C E N T E N N IA L OLYM ­ PIC CONGRESS, PARIS, F R A N C E Contact Internation­ al O lym p ic C om m ittee, Chateau d e Vidy, CH-1007 Lausanne, Switzerland. Tel: 41 21 621 6111. Fax- 41 21 621 6216. S ep tem b er 10-16, 1994. 25TH F1MS W O R LD C O N ­ GRESS O F S P O R T S M EDICINE, ATHENS, GREECE. Abstracts should be submitted before January 31, 1994. For further details contact: O rganization Idea, 24 Vou- lis Street, 10563, Athens, Greece. Tel: 32 42 045, 32 42 529. Fax: 32 21 023. S ep tem b er 16-18, 1994. O R TH O P AE D IC MEDICINE. A N IN TR O D U C TO R Y C O U RSE O N D IA G N O S IS A N D IN JE C TIO N TEC H NIQUES, S A N LUIS OBISPO , CA, USA. For further details contact: T h o m a D orm an MD, Attention: Shirley Hulin, 171 North Santa Rosa Street, S te A, San Luis Obispo, CA93405-1322, USA. O ctob er 3-8, 1994. A U S T R A L IA N SPO R TS M ED ICINE FE D ERATIO N — IN T E R N A T IO N A L C O N F E R E N C E IN S C IE N C E A N D M E D IC IN E IN SPORT, BRISBANE, AU STR ALIA. Contact Australian Sports M edicine Fede­ ration Limited, P O B ox 897, Belconnen A C T 2616, Aus­ tralia. Tel: 06 251 6944. Fax: 06 253 1489. A pril 5-7, 1995. C O N F E R E N C E O N N U TR ITIO N A N D PH YSIC AL ACTIVITY, T O O PTIM IZE PE R F O R M A N C E A N D W ELL-BEING. T h e Ritz-Carlton, Buckhead, Atlan­ ta, Georgia, USA. Contact: M s Lili C Merritt, Internation­ al Life S cien ce Institute, 1126 Sixteenth Street, NW, Washington, DC 20036, USA. Tel: 202 659 0074. Fax: 202 659 3859. May 23-27, 1995. 10TH IN TE R N A TIO N A L SYM POSIUM O N A D A P T E D PHYSICAL ACTIVITY. Contact 10th ISA- PA Secretariat, T h e N orw egian University o f Sport and Physical Education, D epartm ent o f Information, Post- boks 40, Kringsja, N-0807, Oslo, Norway. S ep tem b er 14-17, 1995. T H E XITH F IN A W ORLD SPO R TS M ED IC IN E CONGRESS. Athens Hilton Hotel, Greece. Contact: Public Relations Center, Halen Haly- vides, foz M ichalaropoulou Street, 115-28 Athens, Greece. Tel: (301) 775 6336 — 777 1056. Fax: (301) 771 1289. □ SA JOURNAL OF SPORTS MEDICINE SEPTEMBER 1994 5 R ep ro du ce d by S ab in et G at ew ay u nd er li ce nc e gr an te d by th e P ub lis he r (d at ed 2 01 2. ) The Dynamic Disorders of Skeletal Muscle Metabolism with special reference to Exercise TD Noakes MB ChB MD FACSM Introduction Most o f the skeletal m uscle disorders encountered in clinical m edicine are o f a sufficiently severe nature that they cause such weakness that participation in physical activity is not possible. These degenerative or myopathic disorders cause progressive m uscle weakness and atrophy usually leadin g to death at a relatively young age. However there are a group o f skeletal m uscle disord­ ers which cause sym ptom s only during exercise. These are known as the dynam ic m uscle disorders and are com patible with an unaltered life expectancy. T h ey are o f special interest to sports scientists as the b io ch em i­ cal abnorm alities present in these conditions allow in­ sights into m etab olic factors in skeletal m uscle which influence cardiovascular function during exercise, and to sports physicians because these conditions need to be considered in the differential diagnosis o f exercise- induced syndromes. In addition, the clinical syndrom es o f malignant hyperpyrexia, exercise-induced heatstroke and rhabdom yolysis which acute renal failure are prob­ ably inter-related and m ay be caused by o n e or m ore o f the d ynam ic disorders o f skeletal m u scle m eta b o­ lism, perhaps as yet undefined. This review will em phasize esp ecially the dynam ic skeletal m uscle disorders that cause sym ptom s during exercise. N o attention is paid to the degenerative skele­ tal muscle disorders that cause sym ptom s at rest These conditions are well described in conventional m edical texts and are o f no special interest to sports practition­ ers. It should be em phasized that the dynam ic disord­ ers o f skeletal m uscle m etabolism are exceedingly un­ com m on. T h e intellectual interest they evoke is quite out o f proportion to their clinical importance. Clinical presentation T h e dynam ic disorders o f skeletal m uscle m etabolism are characterized by the follow ing features: First, there are no sym ptom s at rest. In par­ ticular, muscle weakness, a characteristic feature o f the atrophic and destructive m yopathies, is absent. Second, the diagnostic feature is the early on ­ set o f fiatigue — easy fiatigueability — during ex- Liberty Life Chair o f Exercise and Sports Science and M R C / U C T Bioenergetics o f Exercise Research Unit Department of Physiology University o f Cape Town Medical School Observatory South Africa ercise, even when the exercise is o f a m ild in­ tensity. Third, the cardiorespiratory response to exer­ cise is abnorm al with an elevated heart rate, cardiac output and m inute ventilation. Fourth, there m ay b e rhabdom yolysis with m yoglobinuria. If severe, this m ay lead to acute renal failure. Classification Th ere are four subgroups in this category: — Defects o f carbohydrate metabolism, the classic form o f which is M cA rd le’s syndrom e. — D efects o f lipid m etabolism . — D efects o f m itochondrial function. — D efects o f adenine n ucleotide m etabolism . MCARDLE’S SYNDROME In this condition which has its onset early in life, either late childhood or early adulthood, the patient has se­ vere exercise intolerance (M cA rdle, 1951). Th ere is the onset o f m uscle pain and contractures during m ore vigorou s exercise. T h e contractures are electrically si­ lent unlike nocturnal cramps in which there is increased electrical activity. If the exercise is continued, the con ­ tractures m ay lead to ischaem ic d a m a g e o f the m us­ cle leading to m yoglobinuria with possible renal dam age. In less severe cases, there m ay also be m us­ cle swelling and soreness, follow ed after exercise by elevated serum en zym e activities and m yoglobinuria, on occasion. But if the exercise is continued at low intensity, the patient experiences a “ second w ind” in which the pain dim inishes so that he o r she is able to continue exer­ cising albeit at a relative low exercise intensity. Factors that exp ed ite the onset o f the second w ind include e x ­ ercising in warm w eather and the avoidance o f a high carbohydrate m eal shortly before exercise. Factors that aggravate the sym ptom s are obviously the reverse — exercising in the cold and eating a high carbohydrate m eal shortly before exercise. Carbohydrate ingestion causes serum-free fatty acid concentrations to fall there­ by lim iting the availability o f this alternate fuel for the exercising muscles. Factors which reduce skeletal mus­ cle b lo od flo w also delay or prevent the onset o f the second wind. T h e biochem ical hallm ark o f the condition is the failure o f the exercising m uscles to produce appropri­ ate am ounts o f lactate during vigorou s or ischaem ic exercise. M cA rd le (1951) recogn ized the sim ilarity b e ­ tween this clinical picture and the develop m en t o f con- 6 SA JOURNAL O F SPORTS MEDICINE SEPTEMBER 1994 R ep ro du ce d by S ab in et G at ew ay u nd er li ce nc e gr an te d by th e P ub lis he r (d at ed 2 01 2. ) MUSCLE METABOLISM tractures without lactate production by m uscles p o i­ soned with the glycolytic inhibitor iodoacetate. He con­ cluded that patients with this syndrom e must be suffer­ ing from an enzym atic defect in the gly co g en oly tic or glycolytic pathways. Indeed, the absence o f on e or m ore o f the follow ing en zym es have been described in pa­ tients w ith the sym ptom com p lex described by McAr- dle: g ly co g en phosphorylase, g ly c o g e n phosphorylase b kinase, phosphofructokinase, phosphoglycerate kinase, ph osphoglycerate mutase and lactate dehydro­ genase. A ll these enzym e defects reduce the ability o f the cell to produce ATP by oxygen-independent pathways. This is confirm ed by the low levels o f gly colytic interm edi­ ates and pyruvate m easured by m uscle biopsy during exercise in these patients (K on o et al 1984; Wahren et al 1973). In addition, there is an inability to produce pyruvate at a sufficiently fast rate to fuel oxidative m etabolism (Lew is and Haller, 1986). Patients with gly co gen phosphorylase deficien cy are able to oxidize glucose and free fatty acids for en erg y whereas those with en zym e deficiencies below phosphorylase can o x ­ idize only free fatty acids as interruption o f the g ly c o ­ lytic pathway prevents the c om plete m etabolism o f glu­ cose — > pyruvate — > acetyl C o A for further oxida­ tion in the Krebs cycle. Thus whereas the provision o f glucose by infusion will increase the exercise tolerance o f patients with a pure phosphorylase deficiency, such infusions will have no effect on those with en zym e defects in the gly colytic pathway. T h e result o f this inability to supply adequate sub­ strate to the Krebs cy cle for oxidative m etabolism is that, during exercise, there is an abnorm ally large decrease in m uscle PC r concentrations and m uscle pH and a large increase in m uscle Pi concentrations. W hen stimulated electrically, the muscles o f patients with this syndrom e also lose their action potentials, pos­ sibly su ggestin g that glycolytically-produced A T P m ay be required for m aintaining the excitability o f m e m ­ branes esp ecially the sarcolem m a and TTubules. Disturbances o f oxygen transport and cardiac function in patients with M cA rdle’s syndrom e Oxygen transport and utilization M cArdle’s syndrom e had been used as a m odel to study the m etab olic factors in the active skeletal m uscle that influence cardiovascular function (Lew is and Haller, 1986; Lewis et al 1991). It is found that the m axim um oxy gen consum ption (V 0 2 max) o f patients with M cA rdle’s syndrom e is about 18 ml 0 2 K g -1 V iin -1 o r roughly half that found in nor­ mal patients. T h e reduced V 0 2max is not due to re­ duced m uscle mass and is thus distinct from the low VO2 max observed in patients with prim ary m uscle dis­ eases such as muscular dystrophy in which there is m uscle wasting. T h e low V 0 2max o f patients with M cA rd le’s syn­ drom e has been related to the abnorm ally slow rate o f substrate flux through the Krebs cycle and the electron transport chain. T h e inability to fuel the Krebs cycle with pyruvate causes the Krebs cycle to b e c o m e “ run down” . Thus the rate o f form ation o f m itochondrial reducing equivalents (N AD H and FADH2) will ultimately lim it the rates o f oxidative phosphorylation and there­ fore the V 0 2max. Although w hole body V 0 2 is norm al at rest in these patients, at any given w orkload total b o d y V 0 2 is greater than normal. This is explained by an increased oxygen consum ption o f the cardiac and respiratory m uscles due to an excessive tachycardia and elevation o f systolic b lo od pressure and a greater than normal pulm onary ventilation. Respiratory exchange ratios dur­ ing exercise are also abnorm ally low indicating an in­ creased reliance on fat as the m ajor m etabolic fuel for exercise. T h e V 0 2 max o f patients with M cA rd le’s syndrom e is increased by intravenous glucose or lactate infusions. Even then, blood lactate concentrations d o not increase indicating that a m ajor reason for the reduced w ork ca­ pacity o f these patients is a lack o f oxidizable substrate, esp ecially pyruvate, to fuel the Krebs cycle. This also indicates that b lood glu cose cannot fully substitute for m uscle g ly cogen as an oxidative substrate in short-term heavy exercise. Sim ilarly an elevation o f serum -free fatty acid con ­ centrations also increases V 0 2 max by the order o f 18-25%. Thus a lim itation in the availability o f free fat­ ty acids also contributes to the low V 0 2max o f these patients. Cardiovascular function Patients with M cArdle’s syndrom e show an hyperkinetic circulatory response to exercise. T h is hyperkinetic cir­ culatory response is not due to cardiac or vascular dis­ ease; cardiac m uscle is spared in M cA rdle’s disease b e ­ cause o f the presence o f cardiac specific glycogen phos­ phorylase isoenzymes. There is also no evidence for ab­ norm al g ly c o g e n ph osphorylase activity in vascular sm ooth muscle. T h e elevated cardiac output during subm axim al e x ­ ercise is b elieved to result from excessive vasodilata­ tion in the active m uscles possibly related to the large fell in intramuscular PC r and the excessive rise in Pi concentrations This hyperkinetic circulation is partial­ ly norm alized during the infusion o f free fatty acids or during exercise when serum -free fatty acid concentra­ tions are elevated This finding links m echanism s regu­ lating system ic h aem odynam ics and local vasodilata­ tion with the availability o f oxidizable substate to the contracting muscles. Hence it is not only the availabili­ ty o f o xygen that controls peripheral vascular function. Glucose infusion sim ultaneously decreases both the cardiac output and the extent o f the d ecline in PCr and the rise in Pi concentrations during exercise in these patients. This indicates that there is probably a recipro­ cal relationship between skeletal m uscle blood flow and cellular ATP/ADP.Pi ratios (the phosphorylation poten­ tial). This su ggests that the crucial m etab olic conse­ quence o f M cA rdle’s disease is an abnorm ally large d e ­ cline in this ratio in m uscle during exercise. T h e exact vasodilator substances acting in M cA rdle’s syndrom e are not known but increased concentrations o f lactate and hydrogen ions, o r a low arterial P 0 2 o r increased P C 0 2 have all been excluded as n on e is d if­ SA JOURNAL OF SPORTS MEDICINE SEPTEMBER 1994 7 R ep ro du ce d by S ab in et G at ew ay u nd er li ce nc e gr an te d by th e P ub lis he r (d at ed 2 01 2. ) MUSCLE METABOLISM ferent from values m easued in norm al persons. Thus the likely vasodilators are phosphate, potassium and adenosine, the latter derived from AMP. O f these, intra­ muscular phosphate concentrations are known to in­ crease steep ly in these patients during exercise and there is also increased potassium release by muscle. Either or both could b e im portant vasodilators in this disease. Alternatively, these m etabolites m ay stimulate skeletal m uscle (G roup 111 and IV) afferents which then induce the excessive cardiovascular response during ac­ tivity (Lew is et al 1991). In contrast, during static exercise, patients with M c­ A rd le’s syndrom e do not show the expected increase in m uscle sym pathetic nerve activity. Thus, in normal m uscle this reflex is probably activated by increased rates o f glyco gen olysis with a fall in m uscle pH (Pryor et al 1990). Patients with M cA rd le’s syndrom e also show an ab­ normal increase in am m onia production by muscle, fur­ ther indicating/increased A M P production with conse­ quent deam ination to am m on ia and IMP. Glucose in­ fusion also reduces the production o f am m onia; thus a reduction o f am m on ia production m ay also b e a fac­ tor reducing the abnorm al cardiac output in these pa­ tients. Biochemical features o f fatigue in McArdle’s syndrome T h e outstanding observation in these patients is that despite the lim ited capacity o f phosphorylase deficient m uscle to resynthesize ATP, little o r no decline in mus­ cle A T P concentrations has been observed during fatigueing exercise in M cArdle’s patients. However there is an abnorm ally large accum ulation o f Pi and proba­ b ly o f A D P and A M P and these could contribute to fa­ tigue by inhibition o f intracellular processes involved in muscle contraction. Glucose infusion reduces the ex ­ tent to which Pi concentrations rise and increases re­ sistance to fatigue. This indicates a m etabolic shift from the creatine kinase (Equation 1, below ) and myokinase- A M P deam inase coupled reactions (Equation 2, below) in which there is net accum ulation o f phosphate, to those o f oxidative phosphorylation and glycolysis in which both A D P and Pi are used to resynthesize A TP (Lew is and Haller, 1986). Equation 1 T h e creatine kinase reaction A T P - > A D P + Pi A D P + PCr - > A T P + Cr net: PCr - > Pi + Cr Equation 2 T h e m yokinase-AM P deam inase reaction 2 A T P - > 2 A D P + 2Pi 2 A D P - > A M P + ATP A M P - > NH 3 + IMP net: A TP - > 2Pi + NH3 + IM P Thus the abnorm ally large rises in intramuscular Pi con­ centrations during exercise in these patients indicates their reliance on the creatine kinase and the myokinase- A M P deam inase cou pled reactions to regenerate A T P (Equations 1 and 2) rather than o n oxidative m etab o­ lism. T h e detrim ental result is the accum ulation o f in­ creased intracellular Pi concentrations which im pair m uscle contraction and cause fatigue. Th ere is also evid ence that the rate o f A T P turnover is reduced during fatigue in M cA rd le’s patients indicat­ ing product inhibition o f the rate o f ATP hydrolysis This m echanism is thought to explain exercise-induced fa­ tigue also in healthy persons. A decline in skeletal m uscle excitation shown by a fall in the m uscle action potential is also found in these patients. Th is could be the result o f product inhibition o f the m em brane Na + /K + ATPase reaction which can be relieved by the rem oval o f phosphate via gly co gen o l­ ysis in norm al but not in phosphorylase deficient m us­ cle. Lewis and Haller (1986) conclude that events which limit A TP synthesis in M cArdle’s patients also limit ATP hydrolysis, thereby slow ing A TP turnover and prevent­ ing m uscle rigor from developing, analogous to the sit­ uation that develops in norm al m uscle during exhaus­ tive, m axim al exercise. Thus the bioch em ical basis for fatigue in skeletal m uscle in both norm al and diseased m uscle m ay be quite similar. Th ere are two oth er interesting features o f this con ­ dition. First, patients with M cA rd le’s syndrom e show a “ ventilation turnpoint” during exercise indicating that this phenom enon, also known as the “anaerobic thresh­ o ld ” , has no relationship to lactate production by the skeletal muscles. Second, patients with M cA rdle’s syndrom e also show a post-exercise o xy g en debt (excess post-exercise o xy­ gen consum ption — EPO C). Traditional theories have su ggested that the E P O C is due to an excess oxygen consum ption required during the post-exercise recov­ ery period to oxidize the lactate produced during the precedin g exercise. T h e presence o f this ph enom enon in these patients indicates that this cannot b e the cor­ rect explanation. Lactate transporter defect Fishbein (1986) has recently d escribed the first case o f an intriguing and possibly not uncom m on m uscle dis­ order in which there is an absence o f the lactate trans­ porter in both skeletal m uscle and red b lood cells. Th e lactate transporter is b elieved to be a m em bran e pro­ tein that co-transports a lactate anion and a proton e x ­ ternally without a requirem ent for ATP. T h e transporter is thought to b e responsible for 9 0 % o f lactate efflux from these cells. Its activity is sensitive to the pH gra­ dient across the cell m em brane and increases markedly as the intracellular pH falls (Fishbein, 1986). T h e patient described by Fishbein was a 26 year old m ilitary drill instructor w ho was investigated for chest pain and coincidentally found to have m arkedly elevat­ ed serum C K activities (up to 13,700 10 — norm al up to 2 00 10) on several occasions. Exercise tests revealed that the patient showed elevated b lo o d lactate concen­ trations after exercise and was therefore not suffering from M cA rd le’s syndrom e. However the rate at which his blood lactate concentrations returned to the normal resting levels after exercise was profoundly delayed. Laboratory studies confirm ed that the rate o f lactate 8 SA JOURNAL O P SPORTS MEDICINE SEPTEMBER 1994 R ep ro du ce d by S ab in et G at ew ay u nd er li ce nc e gr an te d by th e P ub lis he r (d at ed 2 01 2. ) MUSCLE METABOLISM release from the patient’s red b lo o d cells was also se­ verely abnorm al. W hilst the patient had no sym ptom s directly attri­ butable to this condition, Fishbein suggests that e x ­ trem e exercise in such patients could lead to rhabdo­ m yolysis d ue to their inability to d ecrease intracellular acidosis sufficiently rapidly during and after exercise. Th e condition m ay also explain the frequently unex­ plained fin din g o f chronically elevated serum C K ac­ tivities and attacks o f rhabdom yolysis in s o m e appar­ ently healthy individuals. DEFECTS OF LIPID METABOLISM Th e classic disorder o f lipid m etabolism is that due to the absence o f the e n zy m e carnitine palmityltransfer- ase (C P T ) in skeletal m uscle. This en zym e is essential for the transport o f lon g chain fatty acids across the in­ ner m itochondrial m em brane for their further m etabo­ lism by beta-oxidation with the production o f acetyl- co A which enters the Krebs cycle. To date there have been approxim ately 25 subjects with this condition reported in the literature. Two have been fem ales. Th e inheritance o f the condition is autosomal recessive (An- gelini et al 1981). A related condition is m uscle carnitine deficiency. Carnitine is also essential for the transport o f fatty acids across the m itochondrial m em brane. Carnitine is pro­ duced in the liver and transported to m uscle via b lood from where it is actively absorbed. Carnitine deficiency m ay therefore result from the failure o f carnitine syn­ thesis by the liver or b e due to the failure o f carnitine uptake by the muscles. Treatm ent with carnitine helps those patients who d o not produce carnitine. M uscle C P T exists in two different form s on the in­ ner (CPT-11) and outer (CPT-1) m itochondrial m em branes It is a deficien cy o f CPT-11 which causes this syndrom e (Trevisan et al 1987). Sym p tom s o f C P T d eficien cy usually b eg in late in childhood o r in early adulthood. A s in M cA rd le’s syn­ drom e, there are no abn orm alities at rest but fasting m ay cause serum C K activities to rise m arkedly (Car­ roll et al 1979). Patients are usually able to perform vigorou s exer­ cise without com plications and their VO z max values and cardiovascular function during exercise are normal (Lewis et al 1991). This finding indicates the importance o f normal carbohydrate m etabolism for m axim um exer­ cise and for the norm al cardiovascular response to e x ­ ercise. However m uscle tenderness, pain and sw elling m ay occur after very p rolo n ged exercise. Cramps m ay also b e a feature o f the condition (B y e and Kan, 1988). More gen eralized m uscle sw elling m ay occur when exercise follows a bout o f p rolo n g ed fasting o r after a period on a low carbohydrate, high fat diet. Muscle pain and swell­ ing are accom panied by very m arked elevations in se­ rum enzym e activities and in myoglobinuria. There may also be acute renal failure. Patients with this condition are dependent on carbo­ hydrate to provide their en ergy requirements during ex­ ercise. Thus they bum carbohydrates m ore rapidly than usual during exercise and m ay d evelop rh abdom yoly­ sis when m uscle g ly co gen d ep letion occurs. Prevention o f com plications is therefore through the prescription o f a high carbohydrate diet to maintain muscle and liver gly co gen concentrations. T h e condition can be diagn osed with m uscle biopsy which confirm s the absence o f C P T activity. Lipid-filled vacuoles m ay be shown predom inantly in Type 1 fibres; they are esp ecially m arked in the form o f this con d i­ tion which results from carnitine deficien cy (B y e and Kan, 1988). DEFECTS OF MITOCHONDRIAL FUNCTION Syndromes associated with excessive lactate formation In these patients there are deficien cies in o n e or m ore o f the enzym es o f the electron transport chain; in som e patients no defect has yet been identified. Th e effect o f these abnorm alities is to reduce the capacity for o x ­ idative A T P production and therefore to increase reli­ ance on glycolytic A TP production with increased rates o f lactate and pyruvate production and the associated severe m etab olic a cid osis T h e clinical features com m on to all these conditions are extrem e exercise intolerance associated with early fatigue, m u scle weakness and dyspnoea. T h e patients respond to acute exercise as if they were extrem ely un­ fit. S o m e patients have high resting b lood lactate con ­ centrations; however in all, there is a steep increase in b lo od lactate concentrations at very low levels o f exer­ cise. In co m m on with patients with M cA rd le’s syndrom e these patients also show very low V 0 2max values and an abnorm al cardiovascular response to m ild exercise including a disproportionate cardiac output, tachycardia and ventilation for the appropriate m etabolic rate (Haller et al 1989). T h e m etab olic basis for this is presum ably the sam e as that in M cA rd le’s syndrom e, that is in­ creased intramuscular Pi concentrations due to an ab­ normal reliance on the creatine kinase and myokinase- A M P deam inase cou pled reactions to regenerate A TP in muscles which have an impaired capacity to produce A T P by oxidative m etabolism . Th e inheritance o f these conditions is unique because the m itochondrial D N A , which c od es for the 13 protein com pon ents o f the electron transport chain, is trans­ m itted exclusively by the m oth er (Jones and Round, 1990). Th is su ggests that the m o th er m ay have an in­ ordinate influence on the child’s ability to produce A TP by oxidative pathways (and therefore to becom e a cham ­ pion athlete?). DEFECTS OF ADENINE NUCLEOTIDE METABOLISM Myoadenylate deamine deficiency (MD) Th e enzyme m yoadenylate deam inase (M D ) hydrolyzes the breakdown o f A M P (produced by the m yokinase re­ action) to am m on ia and IM P (E quation 2). A bsen ce o f this en zym e is on e o f the com m on est o f the known m uscle en zym e defects and exists in two form s — the prim ary type which is inherited as a com p lete gen e block in an autosom al recessive pattern and the secon­ dary type which results from m uscle d a m a g e due to other diseases (Fishbein, 1985). SA JOURNAL OF SPORTS MEDICINE SEPTEMBER 1994 9 R ep ro du ce d by S ab in et G at ew ay u nd er li ce nc e gr an te d by th e P ub lis he r (d at ed 2 01 2. ) MUSCLE METABOLISM The enzyme defect is believed by some to explain cramping and exercise intolerance in some individuals, usually in adult to middle-age (Fishbein, 1985). Larger studies, however, have failed to shown any association between symptoms and this enzyme defect (Mercelis et al 1987). It may be that this is an enzyme defect still searching for a disease! REFERENCES Angelini C, Fneddo L, Banistella P, et al. Carnitine palmityl tranferase deficiency: Clinical variability, carrier detection and autosomal reces siue inheritance. Neurology 31: 883-886, 1981. ^ Bye AME, Kan AE. Cramps following exercise. Aust Paediatr J 24 258-259, 1988. Carroll JE, DeVito DC, Brooks MH, Planer GJ, Hagberg JH. Fasting as a provocative test in neuromuscular disease. Metabolism 28: 683-687, 1979. Fishbein WN. Lactate transporter defect: A new disease of muscle. Science 234: 1254-1256, 1986. Fishbein WN. Myoadenylate deaminase deficiency: Inherited and ac­ quired forms. Btochem Med 33: 158-169, 1985. Haller RG, Lewis SF, Estabrook RW, DiMauro S, Servidei S, Foster DW. Exercise intolerance, lactic acidosis, and abnormal cardiopulmo­ nary regulation in exercise associated with adult skeletal muscle cytochrome oxidase deficiency. J Clin Invest 84: 155-161, 1989. Jones DA, Round JM. Skeletal muscle in health and disease. Man­ chester University Press, 1990. Kono N, Mineso I, Sumi S, Shimizu T, Kang J, Nonaka K, Tarui S. Metabolic basis of improved exercise tolerance: muscle phosphory­ lase deficiency after glucagon administration. Neurology 34: 1471-1476, 1984. Lewis SF, Haller RG. The pathophysiology of McArdle's disease: clues to regulation in exercise and fatigue. J App Physiol 61: 391-401, 1986. Lewis SF, Vora S, Haller RG. Abnormal oxidative metabolism and O- transport in muscle phosphofructokinase deficiency. JAppl Physiol 71: 391-398, 1991. McArdle B. Myopathy due to a defect in muscle glycogen breakdown. Clin Sci 10: 13-33, 1951. Mercelis R, Martin JJ, de Barsy T, Van den Berghe G. Myoadenylate deaminase deficiency: absence of correlation with exercise intoler­ ance in 452 muscle biopsies. J Neurol 234: 385-389, 1987. Pryor SL, Lewis SF, Haller RG, et al. Impairment of sympathetic acti­ vation during static exercise in patients with muscle phosphory­ lase deficiency (McArdle's disease). J Clin Invest 85: 1444-1449, 1990. Trevisan CP, Isaya G and Angelini C. Exercise-induced recurrent myo­ globinuria: defective activity of inner carnitine palmitoyltransferase in muscle mitochondria of two patients. Neurology 37: 1184-1188, 1987. Wahren J, Felig P, Havel RJ, Jorfeldt L, Pernow B, Saltin B. Amino acid metabolism in McArdle's syndrome. N Engl J Med 288: 774-777, 1973. □ LETTERS to the EDITOR Readers’ letters concerning articles in the Journal are invited, and will be forwarded to our Editors for consideration for publication. Please post to: Glenbarr Publishers C.C. 25 — Bom pas Road Dunkeld 2 1 9 6 W I1 5 E N A C H 9 3 0 6 2 5 E ®|VoUanenTS TABL ETS Diclophenac sodium 7 5 mg m m v* Geigy 10 SA JOURNAL O F SPORTS MEDICINE SEPTEMBER 1994Re pr od uc ed b y Sa bi ne t G at ew ay u nd er li ce nc e gr an te d by th e P ub lis he r (d at ed 2 01 2. ) Muscle Proteins and the Contractile Properties of Muscle Fibres Kathryn H Myburgh PhD Introduction Muscles are machines which provide the power that is the basis for all vertebrate movement. The mechanical properties o f an active muscle are dependent on many factors such as the shape and size o f the whole mus­ cle, its fibre type, fibre size and length, and the angle o f the fibre-tendon attachment, as well as a variety of neural factors including cortical drive and m otor unit recruitment patterns. However, the force originates at the molecular level from the interaction o f the major muscle proteins, actin and myosin, in the presence of ATP and Ca + + . This review will outline some o f the major discoveries which led to the theories of the mechanism o f force production at this level in skeletal muscle, including the roles played by ATP and Ca + + , and the relationship between force and velocity. It will then discuss factors within a single muscle fibre which influence these contractile properties and which are of particular relevan ce to ex ercise scientists. I. The mechanism of force production Our current understanding o f the mechanism o f force production is based in large part on 3 discoveries made in the 1950’s At that time the band-like structure of muscle was already well described even at the level of the sarcomere, but the function o f the bands was not known. Two important discoveries linking the structure of the sarcomere to its function were (i) that the pattern of the bands is caused by thick and thin filaments1 and (ii) that in those bands where the two types o f fila­ ments overlap, they also interact at regular intervals by means o f bridges.2 The third discovery, which was made at the same time by two different investigators and was published in the same edition o f the presti­ gious journal Nature, was that the filaments themselves do not shorten during contraction. Instead, they appear to slide between one another so that the amount by which they overlap increases during active shortening in a contracting muscle.34 These results led to the for­ mulation o f the sliding filament theory o f cross-bridge interaction during muscle contraction.5 Huxley pro­ posed that force was produced by each projection from the myosin thick filament as it attached to the actin fila­ ment and that the force was related to the kinetic ener­ gy available in the cross-bridge before attachment.5 More than a decade later following many more mechan­ ical experiments performed at faster time resolutions and employing very accurate, quick changes in ten­ sion6 or length,7 Huxley and Simmons8 formulated a MRC/C1CT Bioenergetics o f Exercise Research Unit (JCT Medical School Observatory 7925 second proposal for the mechanism o f force generation by the actomyosin cross-bridge. In the second model, it was proposed that force is generated shortly after at­ tachment as the cross-bridge changes to a more sta­ ble configuration (see Fig. 1: 3a and 3b). This hypothe­ sis requires that the attached cross-bridges exist in two or more configurations (see Fig. 1: 1, 3a and 3b) and that the head can rotate from a 9 0 ° angle to a 45° an­ gle (Fig. 1: 3a to 3b). Indeed, a 4 5 ° orientation o f the cross-bridges had already been shown in electron micrographs o f rigor muscle,9 and there was no rea­ son to believe that the cross-bridge could not rotate through that orientation during a contractile cycle. M A-M Figure 1. A schematic representation o f A T P hydrolysis, release o f the products o f ATP hydrolysis and actomyosin interaction during the contractile cycle. Abbreviations: A = actin; M = myosin; A -M = actomyosin complex; ATP = adenosine triphosphate; A D P = adenosine diphos­ phate; Pi = inorganic phosphate. Steps: 1 - cross-bridge attachment; 2 = phosphate release; 3a and 3b - con­ figurational changes; 4 = A D P release; 5 = A TP bind­ ing; 6 = cross-bridge detachment; 7 = A T P hydrolysis. II. The role of ATP in the cross-bridge t^cle While physiologists and physicists were piecing toge­ ther the structural and mechanical data, biochemists were actively investigating the kinetics o f ATP hydroly­ sis by an ATPase enzyme which is part o f the myosin molecule. It had already been discovered in 1939 that the major muscle protein complex, actin-myosin, (also termed actomyosin), catalysed the hydrolysis o f ATP.10 It was not until 1971 that a scheme was presented by Lymn and Taylor11 which integrated the steps in the chemical splitting o f ATP to AD P and Pi, with a cycli­ cal attachment and detachment o f actin and myosin. SA JOURNAL OF SPORTS MEDICINE SEPTEMBER 1994 11 R ep ro du ce d by S ab in et G at ew ay u nd er li ce nc e gr an te d by th e P ub lis he r (d at ed 2 01 2. ) MUSCLE FIBRES In short, A T P hydrolysis occurs before m yosin attaches to actin (F ig. 1: 7), this is follow ed by attachm ent and form ation o f the actom yosin-AD P-Pi com p lex (Fig. 1: 1). A fter release o f the hydrolysis products, Pi and A D P (Fig. 1: 2 and 4), actin and m yosin rem ain associated (Fig. 1: A-M), probably with the cross-bridge head at an angle o f 45°. Actin and myosin dissociate with the bind­ ing o f A T P to m yosin (Fig. 1: 5 and 6), and once again, A T P hydrolysis occurs in the detach ed state (Fig. 1: 7). It on ly b ecam e apparent later that Pi is released in a separate step before the release o f A D P 12 and that the actomyosin-ADP-Pi com plex (Fig. 1: 1) is relatively weak and produces less force than th e subsequent strong- binding actom yosin-AD P co m p lex (Fig. 1: 3 b ).13 III. The role of Ca++ in the cross-bridge cycle Biochem ical studies o f actomyosin-ATP hydrolysis done in solution have highligh ted different properties o f the m yosin-ATPase enzym e. For exam ple, unlike whole muscle which requires both A TP and C a++ to contract, a mixture o f purified m yosin and purified actin can hy­ drolyse A T P without the presence o f C a ++ in the so­ lution.14 This indicated the presence o f an additional protein, or proteins, that could inhibit the cross-bridge cycle unless calcium was present to rem ove that inhibi­ tory action. Th ese proteins were identified as tropom yo­ sin and the troponin -com plex1516 and b ecam e known as regulatory proteins. A very important early discovery which m ade it possible to define the role o f C a ++ on actual force production in the cross-bridge cycle, was the developm ent o f the so-called “skinned” fibre. By in­ cubating a m uscle fibre in a solution containing 50% glycerol, the m em brane is m ad e perm eab le to ions, sm all m olecu les and even larger m olecules.17 T h e ini­ tiation o f contraction in the skinned fibre is no longer dependent on m em brane depolarisation, but is under control o f the investigator, and is achieved by the addi­ tion o f calcium to the solution bathing the fibre. It was later discovered that the level o f force production, meas­ ured by a force transducer to which on e end o f the skinned fibre is attached, could be varied by varying the concentration o f free calcium .18 T h e characteristic relationship betw een force and calcium ion concentra­ tion (see Fig. 2 ) shows that force is n eglig ib le at pCa 6 (= 1 0 -6 M C a ++) and m axim al around pCa 4 (= 1 0 ~ 4 M C a ++). T h e sigm oid al shape o f the curve indicates that few cross-bridges attach initially, but that there is a large coop erative action betw een adjacent myosin- binding sites on actin, so that force increases steeply from approxim ately pCa 5.5. IV. The force-velocity relationship W hen a skinned fibre is attached to a force transducer on one side and a very rapid servo-controlled m otor arm on the other, it is possible to vary the tension in the fibre by varing the position o f the m otor arm and hence the length o f the fibre. T h e shortening velo city can be determ ined at specific fractions o f the m axim um ten­ sion by several load clam ps in which the tension in the fibre is released to specified levels o f subm axim al ten­ sion and the velocity o f tension redevelopm ent is m eas­ ured. T h e data can b e fitted to the Hill equ ation 19 and the maximal velocity o f shortening (Vmax) is calculated p C a Figure 2. The characteristic relationship between force and calcium ion concentration. Abbreviation: pCa = negative log of calcium concentration in moles e.g. pCa 6 = 70~6 M C a +*. from an extrapolation o f the data to 0 load/0 A cha­ racteristic hyperbolic curve is obtained (see Fig. 3) showing how the velo city o f contraction is m axim al when the load (P) is equal to 0, and slows down as P increases until the velo city is 0 at m axim al load (Po). A t this point, no shortening occurs and Po is analogous to m axim u m isom etric force. ti -O Force (P/Po) Figure 3. The characteristic relationship between force and velocity o f contraction. Abbreviations: P = force; Po = maximum force. V. The effect of muscle fibre type on the mechanics of contraction V.i The characteristics of the basic fibre types T h e basic characteristics o f the contractile cycle d e ­ scribed a bove apply to all m uscles with the banded sar­ com ere structure. But, in 1873 the French physiologist, 12 SA JOURNAL O F SPORTS MEDICINE SEPTEMBER 1994 R ep ro du ce d by S ab in et G at ew ay u nd er li ce nc e gr an te d by th e P ub lis he r (d at ed 2 01 2. ) MUSCLE FIBRES Ranvier, noted that red and white skeletal m uscles have different contractile properties: red m uscles contract slowly, w hile white m uscles contract and relax rapid­ ly.21 This apparently sim p le observation set the stage for num erous physiological, biochem ical and h istolog­ ical studies which aim ed to defin e the properties o f different m ucles and m uscle fibre types. In mammals, w hole m uscles are generally com posed o f various fibre types. Th is h eterogen eity com plicates research studies, but allows for a great deal o f physio­ logical variation. Fortunately, in sm aller m am m als such as mice, rats and cats, the soleus is com p osed alm ost entirely o f red m uscle fibres and the extensor digito- rum longus o f white fibres. Th is m ade it quite sim ple for electrophysiological studies to determ ine clear differ­ ences betw eent those m u scle groups in the properties o f a single twitch contraction and led to general accep­ tance o f the term s slow-twitch and fast-twitch fibres.22 A t around the sam e tim e biochem ical studies showed that the myosin from fast-twitch fibres hydrolysed A TP much faster than did the myosin from slow-twitch mus­ cle23 and histochem ists were able to differentiate b e­ tween different myosin ATPase types (isozym es) due to their differing susceptibility to losing their enzym atic activity at different pH’s.24 (S ee Table 1). A n o th e r ap­ proach was to differentiate betw een the fibre types by determ ining either their resistance to fatigue during im ­ posed stim ulation,25 the num ber o f m itochondria pre­ sent and the oxidative en zym e capacity,26’27 or the g ly ­ cogen co n ten t28 In these ways it was m ade possible to draw up a table o f basic fibre typ e classifications (see Table 1). Interestingly, it was found that all the m uscle fibres activated by the sam e m o to r unit fit into the sam e his- tochem ically determ in ed classification o f fibre type.25 However, the follow ing question arises: can the contrac­ tile characteristics o f each fibre type b e ascribed to a com bination o f the neural activation process and the m etabolic characteristics, or d o the contractile proteins them selves also exert an independent influence? T h e single skinned m uscle fibre is the perfect exp erim en ­ tal m o d el to answer this question since, as m entioned before, the activation is controlled by the investigator. T h e follow ing paragraphs will consider whether fibre type affects peak isom etric force production, velocity o f contraction and the force-pCa curve irrespective o f neural control. V.ii Contractile properties o f the basic fibre ty p e s Early experim ents on a large range o f muscle types and sizes showed that the m axim al force was related to the cross-sectional area o f the m uscle.29 Fibre diam eters o f single m uscles fibres can vary up to 10-fold. T h ere­ fore, measurements o f force or tension must be correct­ ed for cross-sectional area, before differences inherent in the m uscle proteins can be discovered. Early reports found that there w ere no differences in the m axim al force (Po) when expressed relative to the cross-sectional area o f slow- or fast-twitch m uscles30 o r fibres dissect­ ed from purely slow-, or purely fast-twitch m uscles31 (see Fig. 3: both Type 1 and 11 have the sam e Po). In skinned fibres the data on m axim al values o f force per unit o f cross-sectional area in different fibre types are TA B L E I Basic S keletal m u scle fibre ty p e classification s Skeletal Muscle Fibre Types N om enclature Type 1 11A IIB slow fast oxidative- fast oxidative gly co lytic glycolytic S O F O G FG Characteristics: Colour red red white Twitch slow fast fast A TPase activity low high high lost at pH 9.4-10.4 4.4-4.6 4.4 G lycogen content low high high Fatigue resistance high high high Oxidative capacity high high low not consistent and range from indicating no significant difference,32 to higher values in slow-twitch fibres,33 or higher values in fast-twitch fibres.34 Data from human biopsy sam ples w ere in agreem en t with the latter fin d­ ings.35 T h ese discrepancies are m ost likely due to difficulties in the m easurem ent o f the cross-sectional areas o f sin gle fibres. T h e fibre diam eter is not always consistent a lon g the length o f a fib re which has been attached to a force transducer and a sm all error in the m easurem ent o f d iam eter is m ag n ified in the calcula­ tion o f cross-sectional area. However, further technical advances have reopened this question and it is currently under investigation in several laboratories. A lth ou gh the issue o f m axim al force production by different fibre types is not resolved, it is currently ac­ cepted that there are m ost likely no differences between fibre types o f healthy m uscle and this observation is explained by assuming that the num ber o f cross-bridges per unit area o f m uscle is consistent36 and that the force per cross-bridge is the same. A s m entioned in sec­ tion 1, cross-bridges can b e in either a weak, low force (actom yosin-AD P-Pi) (see Fig. 1: 1) or a strong, high force (actom yosin-AD P) state (see Fig. 1: 3b). T h e rela­ tive proportion o f each state could therefore also in­ fluence force production. Recent m echanical data sug­ gest that during a m axim al isom etric contraction in a previously rested muscle, the m ajority o f the cross- bridges are in the strong-binding state.37 But when m uscle is fatigued and the intracellular Pi concentra­ tion is high, m ore cross-bridges are in the weak-binding state and force can be reduced by as much as 3 0 % .20 A lthou gh peak isom etric force is apparently sim ilar in both fibre types, the force develop ed at subm axim al C a ++ concentrations is different for fast- and slow- twitch fibres o f the rat.33’38 Slow-twitch fibres could produce low levels o f force at significantly lower con ­ centrations o f C a++ than fast-twitch fibres. However, a steeper slope o f the force-pCa curve in fast-twitch fibres indicate that once the C a ++ concentration threshold for force developm ent has been reached the fast-twitch fibres develop peak force at a faster rate. T h ese obser­ vations can b e attributed to differences in the calcium sensitivity o f different isoform s o f the regulating pro- SA JOURNAL OF SPORTS MEDICINE SEPTEMBER 1994 13 R ep ro du ce d by S ab in et G at ew ay u nd er li ce nc e gr an te d by th e P ub lis he r (d at ed 2 01 2. ) tein, troponin.38-39 It is interesting to note that the myo­ sin and troponin isoforms change after complete inac­ tivity and weightlessness induced by hind limb susperv sion in a rat model and revert to faster isoforms. indicates that even adult muscle proteins are continu­ ously regulated to adapt to environmental changes As mentioned before, the broad division of fibres into fast- and slow-twitch types is based on their speed contraction. Maximal shortening velocity (Vmax) can be as much as 6-fold higher in fast glycolytic fibres com ­ pared with slow oxidative fibres, while the fast, oxida­ tive fibres have a Vmax only 3-fold higher (see Fig. 3 ) 33 In addition, the shape o f the force-velocity curve is more concave for slow-twitch fibres than fast-twi ch fibres indicating that even at a specific fraction of the maximal force, the velocity is slower in the slow-twitch fibres.34 Since the fibres are already fully activated, these differences are unrelated to Ca + + concentration or Ca++ sensitivity and can therefore be ascribed to the contractile proteins themselves. V.iii Further division o f fibre type based on contractile protein subunits . E v e n though the classification of fibre types in Table I is not simple, for a number of r e a s o n s there are not sufficient categories to take into account all the differ ences that are now a p p a r e n t b e t w e e n m u s c ^ ir e s instance, a type I1C fibre, which can be placed between type 11A and I1B in characteristics was identified in 1970.24 Within a decade, improvements in histoch ical techniques suggested that there were also another MUSCLE FIBRES two distinct subtypes of fast-twitch fibres named IIAC and 11AB.41 Also, comparisons o f biochemical and tochemical classification has shown that types UA and UB fibres do not always c o r r e s p o n d to the FOG and l-