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Scientific article
English

Inhibition of T-type calcium channels protects neurons from delayed ischemia-induced damage

Published inMolecular pharmacology, vol. 68, no. 1, p. 84-89
Publication date2005
Abstract

Intracellular calcium increase is an early key event triggering ischemic neuronal cell damage. The role of T-type voltage-gated calcium channels in the neuronal response to ischemia, however, has never been studied. Using an in vitro model of ischemia-induced delayed cell death in rat organotypic hippocampal slice cultures, we show that T-type calcium channels inhibitors drastically reduce ischemic cell damage. Immunostaining studies reveal the existence of Ca(V)3.1 and Ca(V)3.2 types of low-voltage-activated calcium channels in rat organotypic hippocampal cultures. Low extracellular calcium (100 nM) or increase of intracellular calcium buffering ability by BAPTA-acetoxymethyl ester significantly reduced ischemia-induced neuronal damage. Pharmacological inhibition of the T-type calcium current by mibefradil, kurtoxin, nickel, zinc, and pimozide during the oxygen-glucose deprivation episode provided a significant protection against delayed neuronal death. Mibefradil and nickel exerted neuroprotective effects, not only if administrated during the oxygen-glucose deprivation episode but also in conditions of postischemic treatment. These data point to a role of T-type calcium currents in ischemia-induced, calcium-mediated neuronal cell damage and suggest a possible new pharmacological approach to stroke treatment.

Keywords
  • Animals
  • Brain Ischemia/ metabolism/pathology/ prevention & control
  • Calcium Channel Blockers/ pharmacology
  • Calcium Channels, T-Type/ metabolism
  • Cell Death/drug effects/physiology
  • Cell Line
  • Hippocampus/cytology/drug effects/metabolism
  • Humans
  • Neurons/drug effects/ metabolism
  • Neuroprotective Agents/ pharmacology
  • Organ Culture Techniques
  • Perfusion
  • Rats
Citation (ISO format)
NIKONENKO, Irina et al. Inhibition of T-type calcium channels protects neurons from delayed ischemia-induced damage. In: Molecular pharmacology, 2005, vol. 68, n° 1, p. 84–89. doi: 10.1124/mol.104.010066
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ISSN of the journal0026-895X
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