Stimulation-dependent redistribution of charge movement between unavailable and available states.

A previous study (Stroffekova and Heiny 1997) demonstrated that changes in resting, intracellular free Ca2+ can modulate the amount of charge which is available to move upon depolarization and do excitation-contraction-coupling (E-C coupling). Charge movement reflects voltage-driven conformational changes of the dihydropyridine receptor which couple membrane excitation to Ca2+ release from the sarcoplasmic reticulum (SR) and contractile activation (c.f. review: Melzer et al. 1995). The present study demonstrates that dynamic changes in free Ca2+ that occur in the triadic gap during SR Ca2+ release can likewise produce a stimulation-dependent increase in the amount of available charge. Thus this modulation occurs in the physiological range of Ca2+ changes that occur in the triad during normal muscle activity. The modulation of charge movement by intracellular Ca2+ was rapid and maintained; it occurred within 2-3 suprathreshold depolarizations and remained for 5-10 minutes. It could be prevented by intracellular BAPTA and by depleting the SR of Ca2+, but not by EGTA or agents known to alter ion channel phosphorylation. These results are explained by a model in which a Ca2+ binding site on or near the voltage-sensor is normally populated by Ca2+ ions released into the triadic junction during activity and modulates the distribution of voltage sensors between available and unavailable states.