The role of action potential changes in depolarization-induced failure of excitation contraction coupling in mouse skeletal muscle

Excitation-contraction coupling (ECC) is the process by which electrical excitation of muscle is converted into force generation. Depolarization of skeletal muscle resting potential contributes to failure of ECC in diseases such as periodic paralysis, intensive care unit acquired weakness and possibly fatigue of muscle during vigorous exercise. When extracellular K+ is raised to depolarize the resting potential, failure of ECC occurs suddenly, over a narrow range of resting potentials. Intracellular recordings of action potentials (APs) in individual mouse skeletal muscle fibers during depolarization of the resting potential revealed small APs are still generated at resting potentials at which force production has failed. Simultaneous imaging of Ca2+ transients and recording of APs demonstrated failure to generate Ca2+ transients when APs peaked at potentials more negative than -30 mV. An AP property that closely correlated with failure of the Ca2+ transient was the integral of AP volta...