UCLA

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+ ( $$ {\text{K}}_{\text{o}}^{ + } $$ ) concentration ( $$ [ {\text{K}}^{ + } ]_{\text{o}} $$ ) 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 $$ [ {\text{K}}^{ + } ]_{\text{o}} $$ and membrane potentials. Depolarization resulting from current injection or raised $$ [ {\text{K}}^{ + } ]_{\text{o}} $$ 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 $$ [ {\text{K}}^{ + } ]_{\text{o}} $$ to 10 mM potentiated Ca2+ transients elicited by single and tetanic stimulation, while raising $$ [ {\text{K}}^{ + } ]_{\text{o}} $$ to 15 mM markedly depressed both responses. The effects of 10 mM $$ {\text{K}}_{\text{o}}^{ + } $$ on Ca2+ transients, but not those of 15 mM $$ {\text{K}}_{\text{o}}^{ + } $$ , could be fully reversed by hyperpolarization. The results suggests that the force potentiating effects of 10 mM $$ {\text{K}}_{\text{o}}^{ + } $$ 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 $$ {\text{K}}_{\text{o}}^{ + } $$ on force generation.