American Physiological Society
Journal of Applied Physiology
A consistent observation with fatigue in skeletal muscle is a decline in the amplitude of the myoplasmic Ca2+ transient, which is thought to result primarily from a reduced Ca2+ flux through the ryanodine receptor (RyR1) of the sarcoplasmic reticulum (SR) (Fig. 1). This in turn is thought to contribute to the loss in muscle force and power (2). In the past 20 years, the important proteins at the t-tubule SR junction have been identified (Fig. 1), and considerable progress has been made in understanding the molecular mechanism by which t-tubular charge induces SR Ca2+ release. However, the cellular nature of the disturbance(s) in excitation-contraction coupling (ECC) responsible for the reduced Ca2+ release with fatigue have yet to be elucidated (2). Possibilities include t-tubular dihydropyridine receptor (DHPR) inactivation, a disturbance in the linking process between the DHPR and the RyR1, factors that reduce the open probability or conductance of the RyR1, and/or a decline in SR lumen Ca2+ that reduces the chemical driving force (ΔC) for Ca2+ release. It seems likely that more than one factor is involved. For example, high-intensity contractile activity increases extracellular K+ depolarizing the t-tubular membrane, which can at values less negative than −60 mV inhibit the DHPR. Concurrently, a drop in cell ATP and increase in Mg2+ directly inhibits the RyR1.
Fitts, Robert H., "New Insights on Sarcoplasmic Reticulum Calcium Regulation in Muscle Fatigue" (2011). Biological Sciences Faculty Research and Publications. 595.
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