Canada is known for a great many things: maple syrup, coureur de bois, ice hockey, unfailing politeness, and Tim Hortons coffee. But Canada is also home to some true innovators of muscular and neuromuscular physiology. In this short article, the authors’ salute and honour, by vignette and a select citation, the achievements and accomplishments of a few pioneers. In the opinion of the authors’ the people highlighted here broke ground, gave life, contributed important science that laid foundational principles of muscular and neuromuscular physiology and influenced and gave direction to the careers to the ‘next generation’ of Canadian exercise physiologists. As proud as many Canadians are of claiming actors, singers, and other personalities as our own, as authors we proudly lay claim to these CSEP members as true pionniers canadiens de la physiologie musculaire.
McMaster University historically and presently is an international leader in the field of basic and applied neuromuscular physiology. Dr. J. Duncan MacDougall and Dr. Digby Sale were two avant-gardists of applied muscular and neuromuscular physiology in Canada particularly from the 1970s to the early years of the new millennium. In fact, Dr. MacDougall supervised Digby Sale (a sessional instructor for gymnastics at the time) during his doctoral program. The team of Duncan MacDougall and Digby Sale and their collaborations with John Sutton and others provided many of the foundations in the field.
Over the course of his career, which started at McMaster University in 1970, Dr. Duncan MacDougall established himself as a pioneering integrative exercise physiologist who made significant contributions in the areas of cardiovascular physiology, skeletal muscle metabolism and applied human performance.His contributions cover a broad range of topics and are a direct reflection of Dr. MacDougall’s interest in systems integration. While at McMaster, Dr. MacDougall founded the Human Performance Laboratory, which remains operational (now as the Exercise Metabolism Research Group) to this day and served as the location for much of his work.Dr. MacDougall’s work focused on characterizing exercise-induced and immobilization-induced changes in skeletal muscle ultrastructure, fibre characteristics and metabolic adaptations across a broad range of training status (MacDougall et al., 1980). These studies contributed to the foundation of our knowledge on skeletal muscle fibre characteristics in the untrained state and following adaptation to resistance and endurance exercise. He also had a significant impact on our understanding of skeletal muscle glycogen metabolism (MacDougall et al., 1977) as well as protein metabolism in response to exercise (Fowles et al., 2000; Tarnopolsky et al., 1991).These latter studies helped establish a platform for the study of skeletal muscle protein metabolism, which remains an intense area of research in current exercise physiology labs. As further testament to Dr. MacDougall’s broad interests and impact, he also contributed to our understanding of blood pressure responses during and following exercise (Macdonald et al., 1999; Macdonald et al., 2002). Collectively, his work was transformative to the field of exercise physiology and he served as a mentor to many who have gone on to successful research careers including Dr. Mark Tarnopolsky, Dr. Martin Gibala, and Dr. Stuart Phillips. .
Dr. Digby Sale was and is a recognized international leader in the area of neural adaptation to resistance training, training specificity, post-activation potentiation, and many other aspects of strength training. His various reviews and book chapters on neural adaptations to resistance training (Sale et al., 1983; Sale et al., 1982), and post-activation potentiation (Sale, 2002) have individually garnered numerous citations. Dr. Sale’s papers are still consistently cited in contemporary research. A classic figure that still resurfaces (oftentimes unattributed but certainly showing an axiomatic principle) comes from Dr. Sale’s 1988 review (Sale, 1988). We reproduce that figure here as a small history lesson for those not familiar with when we ‘first knew’ that strength gains with resistance training arose primarily due to neuromuscular adaptations (Figure 1).
The success of scientist is measured not only through their publications, citations, and presentations but their legacy in terms of mentoring, supervising, and motivating graduate students. Dr. Sale directed many successful students who subsequently made important contributions to exercise science internationally. Unfortunately not all can be discussed in this article but it would be remiss to not mention at least some of the well-recognized graduates: Dr. Stephen Alway, presently at West Virginia University, established the role of skeletal fiber proliferation in adult muscle responses to overload (Alway et al., 1988); Dr. David Behm at Memorial University of Newfoundland has published approximately 200 articles on strength and power resistance training, instability and balance, stretching and fatigue; Dr. Philip Chilibeck who is presently at the University of Saskatchewan established an international reputation for his work on nutrition supplement effects on bone (Chilibeck et al., 1996); Dr. Paul Zehr, who is an international leader in neuromuscular physiology at the University of Victoria and an author of several popular books. Dr. Jonathon Fowles, a McMaster grad from the MacDougall-Sale schema presently works at Acadia University where his work in the Exercise is Medicine™ Canada program is well recognized. Dr. Sale, received numerous McMaster University teaching award nominations and awards. His teaching and wry humour impacted thousands of individuals through his teaching and presentations and influenced countless numbers of people internationally with his publications. Dr.’s Sale and MacDougall have recently authored a book entitled The Physiology of Training for High Performance (MacDougall & Sale, 2014). Upon moving to York University in 1977 to join the Department of Physical Education and Athletics, Dr. Enzo Cafarelli established the Human Neuromuscular Laboratory. Dr. Cafarelli used evoked responses of electrical and transcranial magnetic stimulation (TMS) in conjunction with voluntary contractions to explain non-hypertrophic neuromuscular adaptations that contribute to maximal force-producing capacity in humans.
Through a series of elaborately designed fatigue and resistance training studies, research from the Cafarelli laboratory showed that adjustments in antagonist coactivation regulate force decline during fatiguing efforts and force augmentation following training. In as much as the seminal work of Sherrington classified reciprocal inhibition during voluntary contraction, Cafarelli identified that activation of antagonists are mediated through central mechanisms that influence presynaptic inhibition of the 1A afferents (Psek & Cafarelli, 1993; Rothmuller & Cafarelli, 1995). Using caffeine, work from Dr. Cafarelli’s lab clearly highlighted that force sensation and increases in central excitability positively affect maximal voluntary activation, spinal excitability and inevitably endurance time (Walton et al., 2003; Kalmar & Cafarelli, 2004).Work from the Cafarelli lab is key to our understanding of how the central motor pathway does not limit voluntary activation but alters the excitability of agonist and antagonist spinal α-motoneurons to shape maximal force-producing capacity in humans under conditions of fatigue and resistance training.
Dr. Cafarelli’s contributions to Exercise Physiology extend beyond his prolific work on force-producing capacity of the human neuromuscular system. Enzo established the Exercise Neuroscience Group (ENG). The inaugural meeting in 1995 at York University brought together ~20 neuroscientists and trainees that study exercise from Canada and the US. This group continues to meet biannually and has grown to ~70 attendees. The impetus for the meeting remains and continues to encapsulate Dr. Cafarelli’s spirt: an environment where collaborations can be strengthened through students sharing their research with a small group of experts in a professional, personal, and dynamic exchange. Since the 1980s, Dr. Lawrence Spriet (current Chair of Human Health and Nutritional Sciences at the University of Guelph) has been a world leader in understanding the mechanisms by which skeletal muscle metabolism is regulated during exercise and dietary challenges. His research has greatly expanded our understanding of the metabolic basis for muscle fitness through integration of whole body physiological measures with in vitro biochemical assessments of metabolism using the Bergstrom biopsy technique and femoral catheterization in humans, as well as rodent models. In close partnership with Dr. George Heigenhauser at McMaster University, Drs. David Dyck and Arend Bonen at the University of Guelph, and many other Canadian and international colleagues, Dr. Spriet’s investigations have revealed how fundamental relationships between carbohydrate and fat interaction (Dyck et al., 1993) are regulated by precise allosteric and covalent control of key enzymes such as pyruvate dehydrogenase and glycogen phosphorylase (Howlett et al., 1998) amongst others.
The translational relevance of these regulatory steps was always a primary objective and has resulted in a greatly expanded understanding of how muscle fitness is influenced by skeletal muscle metabolic regulation across a spectrum of populations including elite athletes and metabolically diseased populations. In collaboration with Dr. Terry Graham and others, he also explored the mechanisms by which caffeine (Spriet et al., 1992) and other ergogenic aids improve endurance performance through altered muscle metabolism. Indeed, these collective fundamental understandings are now taught at both undergraduate and graduate curriculum around the world. Dr. Spriet’s impact continues to this day. His consistent emphasis on integrative experimentation and understanding regulatory mechanisms in humans continues in his current research as well as the activities of many previous trainees who now serve in a variety of academic and industry sectors. Over a career at the University of Guelph that spanned four decades, including 10 years as a department chair, Dr. Terry Graham conducted innovative studies into the regulation of skeletal muscle energy provision. A long-standing interest was the intermediary metabolism of protein and amino acids (Graham & MacLean, 1992), but Dr. Graham also made significant contributions to our understanding of carbohydrate and lipid metabolism, and in particular the role of glycogen in metabolic control (Graham, 2009). He also conducted applied research on the influence of various dietary and nutraceutical interventions on exercise metabolism and performance (Graham, 2001), including seminal studies on caffeine ingestion in conjunction with his long-time Guelph colleague, Dr. Lawrence Spriet (Graham & Spriet, 1995). Dr. Graham’s interest in the metabolic effects of caffeine extended to clinical work that focused on glycemic control in both healthy individuals and those with cardiometabolic disease (Robinson et al., 2004). Dr. Graham was a committed mentor and facilitated countless research opportunities for his students to visit the laboratories of other international leaders in the field. He maintained strong ties to Copenhagen in particular, a relationship that was borne out of his postdoctoral training with Professor Bengt Saltin, which in turn facilitated a lifelong friendship and many fruitful collaborations over the years. Dr. Howard J. Green was and is an integrative physiologist par-excellence.
Over a four decade-long career at the University of Waterloo Dr. Green changed our view of skeletal muscle adaptation. In fact while formally retired, Professor Emeritus Dr. Green can still be seen around the Waterloo campus and says he still has data that he’s writing up. Howie, as he is known to his friends, has a large scientific ‘footprint’ and his work is a more than impressive legacy. Dr. Green, himself an outstanding ice hockey player, contributed work classifying the fitness and performance characteristics of ice hockey players and how their training affected performance (Green, 1987; Green et al., 2012). Dr. Green also challenged dogma that increases in mitochondrial capacity were necessary for marked changes in substrate utilization (Green et al., 1992). He studied thermoregulation (Helyar et al., 1996), short-term higher intensity sprint exercise training as well short-term training models (Green et al., 1989; Green et al., 2004), studied low frequency fatigue, the sarcoplasmic reticulum ATPase (Sandiford et al., 2004), and many other areas. Dr. Green’s early collaborators included other Canadian physiology pioneers and CSEP members Dr. Richard Hughson, Dr. Jay Thompson, and the late Dr.’s Michael Houston and Michael Sharratt. Dr. Green also spent time in the laboratory of Dr. Dirk Pette and published several papers using the chronic low frequency stimulation model showing the profound plasticity of skeletal muscle (Dux et al., 1990).
A good friend of both Dr. Duncan MacDougall and the late Dr. John Sutton, Howie also enjoyed productive collaborations with these two pioneers. In fact, a perusal of Howie’s publications shows that he had interests, and conducted valuable research, in a number of areas that are too diverse to cover here. Howie mentored and advised a number of respected contemporary researchers including: Dr. Russ Tupling, Dr. Eva Chin, Dr. Stuart Phillips, Dr. Todd Duhamel, Dr. Graham Holloway, Dr. Shelley Sandiford, Dr. Jonathon Fowles, and Dr. Jonathan Schertzer. It would be fair to say that Dr. Green’s appreciation to the integrative nature of exercise and the physiological responses to it show that he was an ‘integrative systems physiologist’ well before that term was even invented. Professor Stephen Hawking may have popularized the phrase, but one of the earliest utterances comes from Sir Isaac Newton in 1676 who said, “If I have seen further, it is by standing on the shoulders of giants”. Those we mention here are, at least in the eyes of the authors, pioneers of muscle physiology and on whose shoulders many of us stand today. That they are Canadian makes us even more proud. As CSEP celebrates 50 years of existence as the recognized Canadian authority in exercise science and prescription, integrating research into best practice, we salute these pioneers as a group that have put Canada on the global exercise science map.
Alway S E, MacDougall J.D., Sale D.G., Sutton J.R., and McComas A.J. 1988. Functional and structural adaptations in skeletal muscle of trained athletes. J Appl Physiol (1985) 64(3): 1114-1120.
Chilibeck P D, Calder A., Sale D.G., and Webber C.E. 1996. Twenty weeks of weight training increases lean tissue mass but not bone mineral mass or density in healthy, active young women. Can J Physiol Pharmacol 74(10): 1180-1185.
Dux L, Green H.J., and Pette D. 1990. Chronic low-frequency stimulation of rabbit fast-twitch muscle induces partial inactivation of the sarcoplasmic reticulum Ca2(+)-ATPase and changes in its tryptic cleavage. Eur J Biochem 192(1): 95-100.
Dyck D J, Putman C.T., Heigenhauser G.J., Hultman E., and Spriet L.L. 1993. Regulation of fat-carbohydrate interaction in skeletal muscle during intense aerobic cycling. Am J Physiol 265(6 Pt 1): E852-E859.
Fowles J R, MacDougall J.D., Tarnopolsky M.A., Sale D.G., Roy B.D., and Yarasheski K.E. 2000. The effects of acute passive stretch on muscle protein synthesis in humans. Can J Appl Physiol 25(3): 165-180.
Graham T E 2001. Caffeine and exercise: metabolism, endurance and performance. Sports Med 31(11): 785-807.
Graham T E 2009. Glycogen: an overview of possible regulatory roles of the proteins associated with the granule. Appl Physiol Nutr Metab 34(3): 488-492.
Graham T E and MacLean D.A. 1992. Ammonia and amino acid metabolism in human skeletal muscle during exercise. Can J Physiol Pharmacol 70(1): 132-141.
Graham T E and Spriet L.L. 1995. Metabolic, catecholamine, and exercise performance responses to various doses of caffeine. J Appl Physiol (1985) 78(3): 867-874.
Green H J 1987. Bioenergetics of ice hockey: considerations for fatigue. J Sports Sci 5(3): 305-317.
Green H J, Batada A., Cole B., Burnett M.E., Kollias H., McKay S. et al. 2012. Muscle cellular properties in the ice hockey player: a model for investigating overtraining? Can J Physiol Pharmacol 90(5): 567-578.
Green H J, Duhamel T.A., Ferth S., Holloway G.P., Thomas M.M., Tupling A.R. et al. 2004. Reversal of muscle fatigue during 16 h of heavy intermittent cycle exercise. J Appl Physiol (1985) 97(6): 2166-2175.
Green H J, Helyar R., Ball-Burnett M., Kowalchuk N., Symon S., and Farrance B. 1992. Metabolic adaptations to training precede changes in muscle mitochondrial capacity. J Appl Physiol (1985) 72(2): 484-491.
Green H J, Jones L.L., Houston M.E., Ball-Burnett M.E., and Farrance B.W. 1989. Muscle energetics during prolonged cycling after exercise hypervolemia. J Appl Physiol (1985) 66(2): 622-631.
Helyar R, Green H., Zappe D., and Sutton J. 1996. Comparative effects of acute volume expansion and short-term training on thermal and cardiovascular responses to prolonged exercise. Can J Physiol Pharmacol 74(9): 1087-1094.
Howlett R A, Parolin M.L., Dyck D.J., Hultman E., Jones N.L., Heigenhauser G.J. et al. 1998. Regulation of skeletal muscle glycogen phosphorylase and PDH at varying exercise power outputs. Am J Physiol 275(2 Pt 2): R418-R425.
Kalmar J M and Cafarelli E. 2004. Central fatigue and transcranial magnetic stimulation: effect of caffeine and the confound of peripheral transmission failure. J Neurosci Methods 138(1-2): 15-26.
Macdonald J R, MacDougall J.D., Interisano S.A., Smith K.M., McCartney N., Moroz J.S. et al. 1999. Hypotension following mild bouts of resistance exercise and submaximal dynamic exercise. Eur J Appl Physiol Occup Physiol 79(2): 148-154.
Macdonald J R, Rosenfeld J.M., Tarnopolsky M.A., Hogben C.D., Ballantyne C.S., and MacDougall J.D. 2002. Post exercise hypotension is not mediated by the serotonergic system in borderline hypertensive individuals. J Hum Hypertens 16(1): 33-39.
MacDougall D & Sale D (2014). The Physiology of Training for High Performance Oxford University Press, New York, NY.
MacDougall J D, Elder G.C., Sale D.G., Moroz J.R., and Sutton J.R. 1980. Effects of strength training and immobilization on human muscle fibres. Eur J Appl Physiol Occup Physiol 43(1): 25-34.
MacDougall J D, Ward G.R., and Sutton J.R. 1977. Muscle glycogen repletion after high-intensity intermittent exercise. J Appl Physiol Respir Environ Exerc Physiol 42(2): 129-132.
Psek J A and Cafarelli E. 1993. Behavior of coactive muscles during fatigue. J Appl Physiol (1985) 74(1): 170-175. Robinson L E, Savani S., Battram D.S., McLaren D.H., Sathasivam P., and Graham T.E. 2004. Caffeine ingestion before an oral glucose tolerance test impairs blood glucose management in men with type 2 diabetes. J Nutr 134(10): 2528-2533.
Rothmuller C and Cafarelli E. 1995. Effect of vibration on antagonist muscle coactivation during progressive fatigue in humans. J Physiol 485 ( Pt 3)): 857-864. PMC1158050
Sale D G 1988. Neural adaptation to resistance training. Med Sci Sports Exerc 20(5 Suppl): S135-S145.
Sale D G 2002. Postactivation potentiation: role in human performance. Exerc Sport Sci Rev 30(3): 138-143.
Sale D G, MacDougall J.D., Upton A.R., and McComas A.J. 1983. Effect of strength training upon motoneuron excitability in man. Med Sci Sports Exerc 15(1): 57-62.
Sale D G, McComas A.J., MacDougall J.D., and Upton A.R. 1982. Neuromuscular adaptation in human thenar muscles following strength training and immobilization. J Appl Physiol Respir Environ Exerc Physiol 53(2): 419-424.
Sandiford S D, Green H.J., Duhamel T.A., Perco J.G., Schertzer J.D., and Ouyang J. 2004. Inactivation of human muscle Na+-K+-ATPase in vitro during prolonged exercise is increased with hypoxia. J Appl Physiol (1985) 96(5): 1767-1775.
Spriet L L, MacLean D.A., Dyck D.J., Hultman E., Cederblad G., and Graham T.E. 1992. Caffeine ingestion and muscle metabolism during prolonged exercise in humans. Am J Physiol 262(6 Pt 1): E891-E898.
Tarnopolsky M A, Atkinson S.A., MacDougall J.D., Senor B.B., Lemon P.W., and Schwarcz H. 1991. Whole body leucine metabolism during and after resistance exercise in fed humans. Med Sci Sports Exerc 23(3): 326-333.
Walton C, Kalmar J., and Cafarelli E. 2003. Caffeine increases spinal excitability in humans. Muscle Nerve 28(3): 359-364.