Effects of membrane depolarization and changes in extracellular K+ on the Ca2+ transients of fast skeletal muscle fibers. Implications for muscle fatigue

摘要

Repetitive activation of skeletal muscle fibers leads to a reduced transmembrane K⁺ gradient. The resulting membrane depolarization has been proposed to play a major role in the onset of muscle fatigue. Nevertheless, raising the extracellular K⁺ () concentration () to 10 mM potentiates twitch force of rested amphibian and mammalian fibers. We used a double Vaseline gap method to simultaneously record action potentials (AP) and Ca²⁺ transients from rested frog fibers activated by single and tetanic stimulation (10 pulses, 100 Hz) at various and membrane potentials. Depolarization resulting from current injection or raised produced an increase in the resting [Ca²⁺]. Ca²⁺ transients elicited by single stimulation were potentiated by depolarization from −80 to −60 mV but markedly depressed by further depolarization. Potentiation was inversely correlated with a reduction in the amplitude, overshoot and duration of APs. Similar effects were found for the Ca²⁺ transients elicited by the first pulse of 100 Hz trains. Depression or block of Ca²⁺ transient in response to the 2nd to 10th pulses of 100 Hz trains was observed at smaller depolarizations as compared to that seen when using single stimulation. Changes in Ca²⁺ transients along the trains were associated with impaired or abortive APs. Raising to 10 mM potentiated Ca²⁺ transients elicited by single and tetanic stimulation, while raising to 15 mM markedly depressed both responses. The effects of 10 mM on Ca²⁺ transients, but not those of 15 mM , could be fully reversed by hyperpolarization. The results suggests that the force potentiating effects of 10 mM might be mediated by depolarization dependent changes in resting [Ca²⁺] and Ca²⁺ release, and that additional mechanisms might be involved in the effects of 15 mM on force generation.