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Neuroscience. 1995 Apr;65(4):1109-18.

Dual action of thapsigargin on calcium mobilization in sensory neurons: inhibition of Ca2+ uptake by caffeine-sensitive pools and blockade of plasmalemmal Ca2+ channels.

Author information

1
Department of General Physiology of the Nervous System, Bogomoletz Institute of Physiology, Kiev, Ukraine.

Abstract

The action of thapsigargin on intracellular calcium homeostasis and voltage-activated calcium currents was studied on freshly isolated adult mouse dorsal root ganglia neurons. The cytoplasmic Ca2+ concentration ([Ca2+]i) was measured using indo-1-based microfluorimetry; transmembrane Ca2+ currents were recorded under voltage-clamp in the whole-cell configuration of the patch-clamp technique. Extracellular applications of thapsigargin at concentrations of 20-2000 nM did not cause substantial changes of basal [Ca2+]i level in the majority of neurons studied. However, 5-10 min incubation of neurons with 20 nM thapsigargin completely and almost irreversibly inhibited caffeine-mediated Ca2+ release from intracellular pools. This inhibition was associated with deceleration of the recovery of depolarization-induced [Ca2+]i transients, presumably due to the inhibition of Ca2+ uptake by intracellular calcium stores. At concentrations between 200 and 2000 nM, thapsigargin markedly depressed the amplitudes of depolarization-triggered [Ca2+]i transients due to the inhibition of transmembrane Ca2+ entry through voltage-activated Ca2+ channels. We found that thapsigargin discriminates between low- and high-voltage-activated Ca2+ channels: 2000 nM of thapsigargin decreased the amplitudes of high-voltage-activated currents by 60%, while the amplitudes of low-voltage-activated Ca2+ currents were reduced by only 25%. Thus, thapsigargin exerts a dual action on [Ca2+]i handling mechanisms in mouse sensory neurons: at low concentrations (< 50 nM) it inhibits Ca2+ accumulation by endoplasmic reticulum pools, whereas at higher concentrations (200-2000 nM) thapsigargin blocks high-voltage-activated Ca2+ currents, reducing Ca2+ entry into the cell.

PMID:
7617166
DOI:
10.1016/0306-4522(94)00553-h
[Indexed for MEDLINE]

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