Ca2+ influx in resting rat sensory neurones that regulates and is regulated by ryanodine-sensitive Ca2+ stores

Yuriy M. Usachev, Stanley A Thayer

Research output: Contribution to journalArticlepeer-review

83 Scopus citations

Abstract

1. Store-operated, voltage-independent Ca2+ channels are activated by depletion of intracellular Ca2+ stores and mediate Ca2+ influx into non-excitable cells at resting membrane potential. We used microfluorimetry, patch-clamp and Mn2+-quench techniques to explore the possibility that a similar mechanism exists in rat dorsal root ganglion (DRG) neurones in primary culture. 2. Following caffeine-induced depletion, ryanodine-sensitive Ca2+ stores refilled with Ca2+ at resting membrane potential. The refilling process required extracellular Ca2+, was blocked by 2 mM Ni2+, and was facilitated by membrane hyperpolarization from -55 to -80 mV, indicating a key role for Ca2+ influx. This influx of Ca2+ was not affected by the voltage-operated Ca2+ channel (VOCC) antagonists nicardipine (10 μM), nimodipine (10 μM) or ω-grammotoxin SIA (1 μM). 3. When ryanodine-sensitive Ca2+ stores were depleted in Ca2+-free media, a return to 2 mM external Ca2+ resulted in a pronounced [Ca2+]1 overshoot, indicating an increased permeability to Ca2+. Depletion of Ca2+ stores also produced a 2-fold increase in the rate of Mn2+ influx. The [Ca2+]1 overshoot and Mn2+ entry were both inhibited by Ni2+, but not by VOCC antagonists. 4. Caffeine induced periodic Ca2+ release from, and reuptake into, ryanodine-sensitive stores. The [Ca2+]1 oscillations were arrested by removal of extracellular Ca2+ or by addition of Ni2+, but they were not affected by VOCC antagonists. Hyperpolarization increased the frequency of this rhythmic activity. 5. These data suggest the presence of a Ca2+ entry pathway in mammalian sensory neurones that is distinct from VOCCs and is regulated by ryanodine-sensitive Ca2+ stores. This pathway participates in refilling intracellular Ca2+ stores and maintaining [Ca2+]1 oscillations and thus controls the balance between intra- and extracellular Ca2+ reservoirs in resting DRG neurones.

Original languageEnglish (US)
Pages (from-to)115-130
Number of pages16
JournalJournal of Physiology
Volume519
Issue number1
DOIs
StatePublished - Aug 15 1999

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