Extra activation component of calcium release in frog muscle fibres

In addition to activating more Ca(2+) release sites via voltage sensors in the t-tubular membranes, it has been proposed that more depolarised voltages enhance activation of Ca(2+) release channels via a voltage-dependent increase in Ca-induced Ca(2+) release (CICR). To test this, release permeability signals in response to voltage-clamp pulses to two voltages, -60 and -45 mV, were compared when Delta[Ca(2+)] was decreased in two kinds of experiments. (1) Addition of 8 mM of the fast Ca(2+) buffer BAPTA to the internal solution decreased release permeability at -45 mV by > 2-fold and did not significantly affect Ca(2+) release at -60 mV. Although some of this decrease may have been due to a decrease in voltage activation at -45 mV - as assessed from measurements of intramembranous charge movement - the results do tend to support a Ca-dependent enhancement with greater depolarisations. (2) Decreasing SR (sarcoplasmic reticulum) Ca content ([Ca(SR)]) should decrease the Ca(2+) flux through an open channel and thereby Delta[Ca(2+)]. Decreasing [Ca(SR)] from > 1000 microM (the physiological range) to < 200 microM decreased release permeability at -45 mV relative to that at -60 mV by > 6-fold, an effect shown to be reversible and not attributable to a decrease in voltage activation at -45 mV. These results indicate a Ca-dependent triggering of Ca(2+) release at more depolarised voltages in addition to that expected by voltage control alone. The enhanced release probably involves CICR and appears to involve another positive feedback mechanism in which Ca(2+) release speeds up the activation of voltage sensors.