All-or-None Ca²⁺Release from Intracellular Stores Triggered by Ca²⁺Influx through Voltage-Gated Ca²⁺Channels in Rat Sensory Neurons

Abstract

Ca2ϩ -induced Ca 2ϩ release (CICR) from intracellular stores amplifies the Ca 2ϩ signal that results from depolarization. In neurons, the amplification has been described as a graded process. Here we show that regenerative CICR develops as an all-or-none event in cultured rat dorsal root ganglion neurons in which ryanodine receptors have been sensitized to Ca 2ϩ by caffeine. We used indo-1-based microfluorimetry in combination with whole-cell patch-clamp recording to characterize the relationship between Ca 2ϩ influx and Ca 2ϩ release. ] i transient. The switch to a suprathreshold response was regulated very precisely in that addition of a single action potential to the stimulus train was sufficient for this transformation. Confocal imaging experiments showed that CICR facilitated propagation of the Ca 2ϩ signal from the plasmalemma to the nucleus. This all-or-none reaction may serve as a switch that determines whether a given electrical signal will be transduced into a local or widespread increase in [Ca 2ϩ ] i .

Painful Nerve Injury Shortens the Intracellular Ca2+ Signal in Axotomized Sensory Neurons of Rats

“…22,23 To measure the contribution of CICR to the Ca 2+ transient after K + depolarization, we treated 17 neurons (3 large, 14 small, with comparable results) with ryanodine (10 μM; fig. 6A).…”

CaMKII inactivation by extracellular Ca2+ depletion in dorsal root ganglion neurons

“…We have observed that removal of Ca 2+ O depletes ryanodine-sensitive stores (both IP 3 R and RyR stores are coupled in DRG neurons [15]). The store-depletion paradigm that we used in these experiments required a prolonged incubation (30- Under physiological conditions, action-potential firing alone is sufficient to partially deplete intracellular stores [39]; however, activity itself activates voltage-gated Ca 2+ -influx pathways. As DRG neurons are not spontaneously active, we utilized the 0 Ca 2+ O paradigm to reproduce store-depletion independent of voltage-gated channel activation.…”

Calcium Regulation in Neuronal Function with Advancing Age: Limits of Homeostasis

“…Neuronal function depends in part on release of calcium from the SER in response to [Ca 2+ ]i elevation (Usachev & Thayer, 1997, 1999a. Rapid calcium buffers immediately dampen much of the calcium influx through voltage-gated calcium channels while rapid release of calcium from the SER sustains depolarization-evoked increases in [Ca 2+ ]i.…”

“…A unique feature of the CICR process, the "all or none" release of calcium from the SER, has been observed in peripheral sensory neurons (Usachev and Thayer, 1997). Using a combination of patch clamp and microfluorometry, [Ca 2+ ]i was elevated with graded step depolarizations of varied time length.…”

“…Despite this rapid calcium buffering, functional signaling is sustained by rapid release of calcium from smooth endoplasmic reticulum (SER) stores. This process has been termed calcium-induced calcium release (CICR) and is mediated by calcium activation of ryanodine receptor (RyR) channels (Belan et al, 1993;Verkhratsky & Shmigol, 1996;Usachev & Thayer, 1997, 1999aVerkhratsky & Petersen, 1998;Akita & Kuba, 2000;Berridge 2002;.…”