ALL-OR-NONE CA2-GATED CA2+ CHANNELS IN RAT SENSORY NEURONS( RELEASE FROM INTRACELLULAR STORES TRIGGERED BY CA2+ INFLUX THROUGH VOLTAGE)

Ca2+-induced Ca2+ release (CICR) from intracellular stores amplifies t he Ca2+ signal that results from depolarization. In neurons, the ampli fication has been described as a graded process. Here we show that reg enerative CICR develops as an all-or-none event in cultured rat dorsal root ganglion neurons in which ryanodine receptors have been sensitiz ed to Ca2+ by caffeine. We used indo-1-based microfluorimetry in combi nation with whole-cell patch-clamp recording to characterize the relat ionship between Ca2+ influx and Ca2+ release. Regenerative release of Ca2+ was triggered when action potential-induced Ca2+ influx increased the intracellular Ca2+ concentration ([Ca2+](i)) above threshold. The threshold was modulated by caffeine and intraluminal Ca2+. A relative refractory period followed CICR. The pharmacological profile of the r esponse was consistent with Ca2+ influx through voltage-gated Ca2+ cha nnels triggering release from ryanodine-sensitive stores. The activati on of a suprathreshold response increased more than fivefold the ampli tude and duration of the [Ca2+](i) transient. The switch to a suprathr eshold response was regulated very precisely in that addition of a sin gle action potential to the stimulus train was sufficient for this tra nsformation. Confocal imaging experiments showed that CICR facilitated propagation of the Ca2+ signal from the plasmalemma to the nucleus. T his all-or-none reaction may serve as a switch that determines whether a given electrical signal will be transduced into a local or widespre ad increase in [Ca2+](i).