Am J Physiol Cell Physiol 299: C891-C902, 2010. First published August 4, 2010; doi:10.1152/ajpcell.00180.2010
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Muscle Cell Biology and Cell Motility
Benjamin L. Prosser,1 Erick O. Hern?ndez-Ochoa,2 Richard M. Lovering,3 Zoita Andronache,4 Danna B. Zimmer,5 Werner Melzer,4 and Martin F. Schneider2 1Center for Biomedical Engineering and Technology (BioMET), 2Department of Biochemistry and Molecular Biology, 3Department of Physiology, University of Maryland, Baltimore, Maryland; 4Institute of Applied Physiology, Ulm University, Ulm, Germany; 5Department of Veterinary Pathobiology, College of Veterinary Medicine and Integrative Biosciences, Texas A&M University, College Station, Texas
Submitted 14 May 2010 ; accepted in final form 2 August 2010
The role of S100A1 in skeletal muscle is just beginning to be elucidated. We have previously shown that skeletal muscle fibers from S100A1 knockout (KO) mice exhibit decreased action potential (AP)-evoked Ca2+ transients, and that S100A1 binds competitively with calmodulin to a canonical S100 binding sequence within the calmodulin-binding domain of the skeletal muscle ryanodine receptor. Using voltage clamped fibers, we found that Ca2+ release was suppressed at all test membrane potentials in S100A1–/– fibers. Here we examine the role of S100A1 during physiological AP-induced muscle activity, using an integrative approach spanning AP propagation to muscle force production. With the voltage-sensitive indicator di-8-aminonaphthylethenylpyridinium, we first demonstrate that the AP waveform is not altered in flexor digitorum brevis muscle fibers isolated from S100A1 KO mice. We then use a model for myoplasmic Ca2+ binding and transport processes to calculate sarcoplasmic reticulum Ca2+ release flux initiated by APs and demonstrate decreased release flux and greater inactivation of flux in KO fibers. Using in vivo stimulation of tibialis anterior muscles in anesthetized mice, we show that the maximal isometric force response to twitch and tetanic stimulation is decreased in S100A1–/– muscles. KO muscles also fatigue more rapidly upon repetitive stimulation than those of wild-type counterparts. We additionally show that fiber diameter, type, and expression of key excitation-contraction coupling proteins are unchanged in S100A1 KO muscle. We conclude that the absence of S100A1 suppresses physiological AP-induced Ca2+ release flux, resulting in impaired contractile activation and force production in skeletal muscle.
S100; excitation-contraction coupling; calcium signaling; muscle
Address for reprint requests and other correspondence: M. F. Schneider, 108 N. Greene St., Baltimore, MD 21201 (e-mail: mschneid{at}umaryland.edu ). Copyright ? 2010 by the American Physiological Society.
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