Mechanisms of intercellular calcium signaling in glial cells studied with dantrolene and thapsigargin

Mechanisms of intercellular calcium signaling in glial cells studied with dantrolene and... Mechanical stimulation of a single cell in a primary mixed glial cell culture induced a wave of increased intracellular calcium concentration ((Ca2+)i) that was communicated to surrounding cells. Following propagation of the Ca2+ wave, many cells showed asynchronous oscillations in (Ca2+)i. Dantrolene sodium (10 μM) inhibited the increase in (Ca2+)i associated with this Ca2+ wave by 60‐80%, and prevented subsequent Ca2+ oscillations. Despite the markedly decreased magnitude of the increase in (Ca2+)i, the rate of propagation and the extent of communication of the Ca2+ wave were similar to those prior to the addition of dantrolene. Thapsigargin (10 nM to 1 μM) induced an initial increase in (Ca2+)i ranging from 100 nM to 500 nM in all cells that was followed by a recovery of (Ca2+)i to near resting levels in most cells. Transient exposure to thapsigargin for 2 min irreversibly blocked communication of a Ca2+ wave from the stimulated cell to adjacent cells. Glutamate (50 μM) induced an initial increase in (Ca2+)i in most cells that was followed by sustained oscillations in (Ca2+)i in some cells. Dantrolene (10 μM) inhibited this initial (Ca2+)i increase caused by glutamate by 65‐90% and abolished subsequent oscillations. Thapsigargin (10 nM to 1 μm) abolished the response to glutamate in over 99% of cells. These results suggest that while both dantrolene and thapsigargin inhibit intracellular Ca2+ release, only thapsigargin affects the mechanism that mediates intercellular communication of Ca2+ waves. These findings are consistent with the hypothesis that inositol trisphosphate (IP3) mediates the propagation of Ca2+ waves whereas Ca2+ ‐induced Ca2+ release amplifies Ca2+ waves and generates subsequent Ca2+ oscillations. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Glia Wiley

Mechanisms of intercellular calcium signaling in glial cells studied with dantrolene and thapsigargin

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Publisher
Wiley
Copyright
Copyright © 1993 Wiley‐Liss, Inc.
ISSN
0894-1491
eISSN
1098-1136
DOI
10.1002/glia.440070203
pmid
8094375
Publisher site
See Article on Publisher Site

Abstract

Mechanical stimulation of a single cell in a primary mixed glial cell culture induced a wave of increased intracellular calcium concentration ((Ca2+)i) that was communicated to surrounding cells. Following propagation of the Ca2+ wave, many cells showed asynchronous oscillations in (Ca2+)i. Dantrolene sodium (10 μM) inhibited the increase in (Ca2+)i associated with this Ca2+ wave by 60‐80%, and prevented subsequent Ca2+ oscillations. Despite the markedly decreased magnitude of the increase in (Ca2+)i, the rate of propagation and the extent of communication of the Ca2+ wave were similar to those prior to the addition of dantrolene. Thapsigargin (10 nM to 1 μM) induced an initial increase in (Ca2+)i ranging from 100 nM to 500 nM in all cells that was followed by a recovery of (Ca2+)i to near resting levels in most cells. Transient exposure to thapsigargin for 2 min irreversibly blocked communication of a Ca2+ wave from the stimulated cell to adjacent cells. Glutamate (50 μM) induced an initial increase in (Ca2+)i in most cells that was followed by sustained oscillations in (Ca2+)i in some cells. Dantrolene (10 μM) inhibited this initial (Ca2+)i increase caused by glutamate by 65‐90% and abolished subsequent oscillations. Thapsigargin (10 nM to 1 μm) abolished the response to glutamate in over 99% of cells. These results suggest that while both dantrolene and thapsigargin inhibit intracellular Ca2+ release, only thapsigargin affects the mechanism that mediates intercellular communication of Ca2+ waves. These findings are consistent with the hypothesis that inositol trisphosphate (IP3) mediates the propagation of Ca2+ waves whereas Ca2+ ‐induced Ca2+ release amplifies Ca2+ waves and generates subsequent Ca2+ oscillations.

Journal

GliaWiley

Published: Feb 1, 1993

References

  • A model of propagating calcium‐induced calcium release mediated by calcium diffusion
    Backx, Backx; de Tombe, de Tombe; van Deen, van Deen; Mulder, Mulder; ter Keurs, ter Keurs
  • Dantrolene prevents glutamate cytotoxicity and Ca 2+ release from intracellular stores in cultured cerebral cortical neurons
    Frandsen, Frandsen; Schousboe, Schousboe
  • Preparation of separate astroglial and oligodendroglial cell cultures from rat cerebral tissue
    McCarthy, McCarthy; Vellis, Vellis
  • Calcium channels, stores, and oscillations
    Tsien, Tsien; Tsien, Tsien

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