B.S. 1967, State University of New York-Cortland
M.A. 1969, University of Buffalo, Buffalo, NY
Ph.D. 1972, University of Wisconsin-Madison
Postdoctoral Fellow, Washington University, St. Louis, MO
The laboratory's primary goals are to understand how skeletal muscle function is altered by programs of regular exercise-training, and elucidate the cellular causes of fatigue. Our work centers on developing a detailed understanding of the cellular processes of excitation-contraction coupling (ECC). In particularly, the signaling between the t-tubular charge sensor [dihydropyridine receptor (DHPR)], and the sarcoplasmic reticulum (SR) calcium release channel (known as the ryanodine receptor, RyR1), and how this coupling is altered in fatigue and programs of exercise-training. A second emphasis is the cross-bridge events responsible for the generation of force, velocity, and power, and how these are altered by programs of exercise and fatigue. We have recently begun to study the role of regular exercise in improving the functional capacity of the whole heart and isolated single myocytes.
Our research effort is directed primarily on two projects: (1) the etiology of muscle fatigue, and (2) the role of high resistance and endurance exercise in improving heart cell function. Our fatigue studies have centered on 2 processes: 1) the role of deleterious changes in ECC in the development low frequency fatigue (LFF); and 2) the effect of inorganic phosphate (Pi), H+, ADP, and myosin light chain phosphorylation on the force and power production of isolated single fibers.
LFF is characterized as a loss of force at low frequencies of activation (10-20 Hz) while force in response to high frequency stimulation (100-150 Hz) is normal. Since muscles are normally activated in vivo at low frequencies, elucidating the cause of LFF has important implications to preventing respiratory muscle failure in disease states such as chronic obstructive pulmonary disease (COPD), and heart failure. The etiology of LFF is thought to involve inhibition of the RyR1 leading to a reduced release of Ca2+ from the SR and less activation of the myofilaments. Currently, we are using in situ and in vitro models to study the hypotheses that LFF results from uncoupling of the DHPR and RyR1, and to factors such as excessive phosphorylation that directly inhibit the RyR1. These studies utilize voltage clamped rat and mouse fibers. Our cross-bridge studies have concentrated on the role of Pi and H+ in inhibiting force and power. Currently, we are studying the kinetic properties of the transition step between the low- and high-force states of the cross-bridge. Details of our Pi and H+ experiments can be found in our publications (see list below).
Heart disease is the leading cause of morbidity and mortality in the western world. Programs of regular exercise-training have been shown to improve coronary circulation, and reduce the incidences and severity of ischemic heart disease. However, the cell and molecular mechanisms of the exercise-induced protection are unknown. As a first step in addressing these issues, we have employed the working heart preparation where the coronary arteries are back perfused via the aorta and heart function studied (Langendorff preparation). Experiments are currently in progress extending this work to isolated single myocytes. Our goal is to determine the cellular mechanism whereby regular exercise protects against ischemic heart disease, and reduces the loss of left ventricular function (i.e. cell death) following regional ischemia.
Nelson, C. R., E. P. Debold, and R.H. Fitts. 2014. Phoshate and acidosis act synergistically to depress peak power in rat muscle fibers." American Journal of Physiology: Cell Physiology 307: C939-C950.
Nelson, C. R. and R.H. Fitts. 2014. Effects of low cell pH and elevated inorganic phosphate on the pCa-force relationship in single muscle fibers at near-physiological temperatures. American Journal of Physiology: Cell Physiology 306: C670-C678.
Manno, C., Figueroa, L., Fitts, R., and Rios, E. 2013. Confocal imaging of transmembrane voltage by SEER of di-8-ANEPPS. J. Gen. Physiol. 141(3): 371-87.
Kent-Braun, J.A., R.H. Fitts, and A. Christie. 2012. Skeletal Muscle Fatigue. Compr Physiol. 2:997-1044.
Fitts, R.H. 2011. New insights on sarcoplasmic reticulum calcium regulation in muscle fatigue. J Appl Physiol. 111:345-346.
Fitts, R.H. 2011. Chapter 6. The Muscular System: Fatigue Processes. In: Advanced Exercise Physiology, 2nd Edit. P. Farrell, Pub Lippincott Williams & Wilkins.
Fitts, R.H., P.A. Colloton, J.G. Romatowski, J.R. Peters, S.W. Trappe, D.L. Costill, J.L. Bain, and D.A. Riley. 2010. Prolonged Space Flight-Induced Alterations in the Structure and Function of Human Skeletal Muscle Fibres. J. Physiol. (Lond). 588: 3567-3592.
Fitts, R.H. 2008. The Cross-Bridge Cycle and Skeletal Muscle Fatigue. J. Appl. Physiol. 104: 551-558.
Knuth, S.T., H. Dave, J.R. Peters, and R.H. Fitts. 2006. Low cell pH depresses peak power in rat skeletal muscle fibres at both 30 and 15 degrees centigrade: Implications for muscle fatigue. J. Physiol. 575: 887-899.
Debold, E.P., J. Romatowski, and R.H. Fitts. 2006. The depressive effect of Pi on the force-calcium relationship in skinned single muscle fibers is temperature dependent. Am. J. Physiol. Cell Physiol. 290: C1041-C1050.
Lawrence G. Haggerty Faculty Award for Research Excellence (2001)
Wehr Distinguished Professor of Biological Sciences (1997-2003)
Marquette Chapter Sigma Xi Distinguished Research Award (1995)
American College of Sports Medicine Citation Award for Research Excellence (1998)
American Journal of Physiology Classic Paper Award (2007)
Xinrui Wang (Ph.D. student)
Dr. Fitts is NOT currently accepting new Ph.D. students into his lab