Effects of calcium channel antagonists on calcium entry and glutamate release from cultured rat cerebellar granule cells

J Neurochem. 1995 Dec;65(6):2517-24. doi: 10.1046/j.1471-4159.1995.65062517.x.

Abstract

Using a range of Ca2+ channel blockers we have investigated the Ca2+ channel subtypes that mediate the depolarisation-induced elevation of the intracellular free Ca2+ concentration ([Ca2+]i) and glutamate release from cultured rat cerebellar granule cells. omega-Conotoxin-GVIA had little effect on either the transient or plateau phase of the depolarisation-induced [Ca2+]i rise or on glutamate release, ruling out a significant role for N-type Ca2+ channels. Nifedipine substantially inhibited the initial transient rise in [Ca2+]i and the plateau phase of the [Ca2+]i rise and glutamate release, suggesting the involvement of L-type Ca2+ channels. Both omega-agatoxin and omega-conotoxin-MVIIC also inhibited the transient rise in [Ca2+]i and glutamate release but not the plateau phase of the [Ca2+]i rise. The inhibitions by nifedipine were not increased by coaddition of omega-conotoxin-MVIIC, suggesting overlapping sensitivity to these channel blockers. These data show that glutamate release from granule cells in response to depolarisation with a high KCI level involves Ca2+ currents that are sensitive to nifedipine, omega-agatoxin-IVA, and also omega-conotoxin-MVIIC. The overlapping sensitivity of the channels to these toxins prevents attribution of any of the phases of the [Ca2+]i rise or glutamate release to distinct P-, Q-, or O-type Ca2+ currents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Calcium Channel Blockers / pharmacology*
  • Calcium Channels / physiology
  • Cells, Cultured
  • Cerebellum / cytology
  • Cerebellum / drug effects
  • Cerebellum / metabolism*
  • Electrophysiology
  • Fluorometry
  • Fura-2
  • Glutamic Acid / metabolism*
  • Intracellular Membranes / metabolism
  • Neurons / drug effects
  • Neurons / metabolism*
  • Peptides / pharmacology
  • Rats
  • Rats, Wistar
  • Spider Venoms / pharmacology
  • omega-Agatoxin IVA
  • omega-Conotoxins*

Substances

  • Calcium Channel Blockers
  • Calcium Channels
  • Peptides
  • Spider Venoms
  • omega-Agatoxin IVA
  • omega-Conotoxins
  • omega-conotoxin-MVIIC
  • Glutamic Acid
  • Calcium
  • Fura-2