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Ca 2+ influx in resting rat sensory neurones that regulates and is regulated by ryanodine‐sensitive Ca 2+ stores
Author(s) -
Usachev Yuriy M.,
Thayer Stanley A.
Publication year - 1999
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.1999.0115o.x
Subject(s) - ryanodine receptor , chemistry , hyperpolarization (physics) , biophysics , extracellular , membrane potential , voltage dependent calcium channel , calcium , intracellular , medicine , endocrinology , biochemistry , biology , stereochemistry , nuclear magnetic resonance spectroscopy , organic chemistry
1 Store‐operated, voltage‐independent Ca 2+ channels are activated by depletion of intracellular Ca 2+ stores and mediate Ca 2+ influx into non‐excitable cells at resting membrane potential. We used microfluorimetry, patch‐clamp and Mn 2+ ‐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 Ca 2+ stores refilled with Ca 2+ at resting membrane potential. The refilling process required extracellular Ca 2+ , was blocked by 2 mM Ni 2+ , and was facilitated by membrane hyperpolarization from −55 to −80 mV, indicating a key role for Ca 2+ influx. This influx of Ca 2+ was not affected by the voltage‐operated Ca 2+ channel (VOCC) antagonists nicardipine (10 μM), nimodipine (10 μ m ) or ω‐grammotoxin SIA (1 μ m ). 3 When ryanodine‐sensitive Ca 2+ stores were depleted in Ca 2+ ‐free media, a return to 2 mM external Ca 2+ resulted in a pronounced [Ca 2+ ] i overshoot, indicating an increased permeability to Ca 2+ . Depletion of Ca 2+ stores also produced a 2‐fold increase in the rate of Mn 2+ influx. The [Ca 2+ ] i overshoot and Mn 2+ entry were both inhibited by Ni 2+ , but not by VOCC antagonists. 4 Caffeine induced periodic Ca 2+ release from, and reuptake into, ryanodine‐sensitive stores. The [Ca 2+ ] i oscillations were arrested by removal of extracellular Ca 2+ or by addition of Ni 2+ , but they were not affected by VOCC antagonists. Hyperpolarization increased the frequency of this rhythmic activity. 5 These data suggest the presence of a Ca 2+ entry pathway in mammalian sensory neurones that is distinct from VOCCs and is regulated by ryanodine‐sensitive Ca 2+ stores. This pathway participates in refilling intracellular Ca 2+ stores and maintaining [Ca 2+ ] i oscillations and thus controls the balance between intra‐ and extracellular Ca 2+ reservoirs in resting DRG neurones.