Calcium influx via L‐type voltage‐gated channels mediates the delayed, elevated increases in steady‐state c‐ fos mRNA levels in cerebellar granule cells exposed to excitotoxic levels of glutamate

Calcium influx via L‐type voltage‐gated channels mediates the delayed, elevated increases in... The altered kinetics of steady‐state c‐fos mRNA production in cultured cerebellar granule cells under excitotoxic conditions was investigated in neurons subjected to depolarising stimuli, namely, high KCl and L‐glutamate (Glu), in which Ca2+ influx occurs by differing routes. Increases in intracellular‐free calcium levels ((Ca2+)i) stimulated by nontoxic or toxic levels of Glu were blocked by selective N‐methyl‐D‐aspartate (NMDA) receptor antagonism; were blocked only partially by the L‐type channel blocker, nifedipine; and were unaffected by α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionate (AMPA)/kainate receptor antagonists. Glu‐induced cell death was prevented only by NMDA receptor blockade. Exposure of cells to nontoxic levels of Glu resulted in a transient increase in c‐fos mRNA levels, whereas an excitotoxic dose produced a delay in the appearance of c‐fos mRNA but a subsequent, progressive, and sustained (>4 hr) increase. An excitotoxic dose of Glu in combination with either nifedipine or selective NMDA receptor antagonists resulted in the normal, transient increase of c‐fos mRNA levels. Chronic exposure to 55 mM KCl caused no cytotoxicity, although it resulted in a delayed, elevated increase in c‐fos mRNA levels that was unaffected by NMDA receptor blockade but reverted to the normal, transient profile of c‐fos mRNA formation when it was coadministered with nifedipine. The KCl‐induced increase in (Ca2+)i levels was inhibited dramatically by nifedipine but was unaffected by any of the ionotropic Glu receptor antagonists. The results support the notion that the appearance of a delayed but elevated increase in steady‐state c‐fos mRNA levels following exposure to excitotoxic doses of Glu is mediated specifically by calcium influx via L‐type voltage‐gated channels. J. Neurosci. Res. 52:641–652, 1998. © 1998 Wiley‐Liss, Inc. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Neuroscience Research Wiley

Calcium influx via L‐type voltage‐gated channels mediates the delayed, elevated increases in steady‐state c‐ fos mRNA levels in cerebellar granule cells exposed to excitotoxic levels of glutamate

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Publisher
Wiley
Copyright
Copyright © 1998 Wiley‐Liss, Inc.
ISSN
0360-4012
eISSN
1097-4547
D.O.I.
10.1002/(SICI)1097-4547(19980615)52:6<641::AID-JNR3>3.0.CO;2-8
Publisher site
See Article on Publisher Site

Abstract

The altered kinetics of steady‐state c‐fos mRNA production in cultured cerebellar granule cells under excitotoxic conditions was investigated in neurons subjected to depolarising stimuli, namely, high KCl and L‐glutamate (Glu), in which Ca2+ influx occurs by differing routes. Increases in intracellular‐free calcium levels ((Ca2+)i) stimulated by nontoxic or toxic levels of Glu were blocked by selective N‐methyl‐D‐aspartate (NMDA) receptor antagonism; were blocked only partially by the L‐type channel blocker, nifedipine; and were unaffected by α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionate (AMPA)/kainate receptor antagonists. Glu‐induced cell death was prevented only by NMDA receptor blockade. Exposure of cells to nontoxic levels of Glu resulted in a transient increase in c‐fos mRNA levels, whereas an excitotoxic dose produced a delay in the appearance of c‐fos mRNA but a subsequent, progressive, and sustained (>4 hr) increase. An excitotoxic dose of Glu in combination with either nifedipine or selective NMDA receptor antagonists resulted in the normal, transient increase of c‐fos mRNA levels. Chronic exposure to 55 mM KCl caused no cytotoxicity, although it resulted in a delayed, elevated increase in c‐fos mRNA levels that was unaffected by NMDA receptor blockade but reverted to the normal, transient profile of c‐fos mRNA formation when it was coadministered with nifedipine. The KCl‐induced increase in (Ca2+)i levels was inhibited dramatically by nifedipine but was unaffected by any of the ionotropic Glu receptor antagonists. The results support the notion that the appearance of a delayed but elevated increase in steady‐state c‐fos mRNA levels following exposure to excitotoxic doses of Glu is mediated specifically by calcium influx via L‐type voltage‐gated channels. J. Neurosci. Res. 52:641–652, 1998. © 1998 Wiley‐Liss, Inc.

Journal

Journal of Neuroscience ResearchWiley

Published: Jun 15, 1998

References

  • Ca 2+ ‐dependent regulation in neuronal gene expression
    Bito, Bito; Deisseroth, Deisseroth; Tsien, Tsien
  • Calcium regulation of gene expression: The mode of entry matters
    Gallin, Gallin; Greenberg, Greenberg
  • Neuronal expression of AP‐1 proteins in excitotoxic‐neurodegenerative disorders and following nerve fiber lesions
    Gass, Gass; Herdegen, Herdegen
  • Association of c‐fos mRNA expression and excitotoxicity in primary cultures of mouse neocortical and cerebellar neurons
    Griffiths, Griffiths; Malcolm, Malcolm; Ritchie, Ritchie; Frandsen, Frandsen; Schousboe, Schousboe; Scott, Scott; Rumsby, Rumsby; Meredith, Meredith
  • Calcium‐mediated mechanisms in chemically induced cell death
    Nicotera, Nicotera; Bellomo, Bellomo; Orrenius, Orrenius
  • Glutamate and the pathophysiology of hypoxic‐ischemic brain damage
    Rothman, Rothman; Olney, Olney
  • Cascade of gene expression induced by Ca 2+ signals in neurons
    Tsuda, Tsuda

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