All-or-none Ca2+ release from intracellular stores triggered by Ca2+ influx through voltage-gated Ca2+ channels in rat sensory neurons.
Ca2+-induced Ca2+ release (CICR) from intracellular stores amplifies the Ca2+ 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 Ca2+ by caffeine. We used indo-1-based microfluorimetry in combination with whole-cell patch-clamp recording to characterize the relationship 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 response was consistent with Ca2+ influx through voltage-gated Ca2+ channels triggering release from ryanodine-sensitive stores. The activation of a suprathreshold response increased more than fivefold the amplitude and duration of the [Ca2+]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 Ca2+ 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 [Ca2+]i.
Usachev
Y M
YM
Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA.
Thayer
S A
SA
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D002478:Cells, Cultured; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D004056:Differential Threshold; D004594:Electrophysiology; D005727:Ganglia, Spinal / Q000166:cytology; D007425:Intracellular Membranes / Q000378:metabolism*; D015640:Ion Channel Gating; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism*; D009994:Osmolar Concentration; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time
D015220:Calcium Channels; D000697:Central Nervous System Stimulants; D002110:Caffeine; D002118:Calcium