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

Nikonenko, Irina
Bancila, M.
Bloc, A.
Bijlenga, P.
Published in Molecular Pharmacology. 2005, vol. 68, no. 1, p. 84-89
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 AnimalsBrain Ischemia/ metabolism/pathology/ prevention & controlCalcium Channel Blockers/ pharmacologyCalcium Channels, T-Type/ metabolismCell Death/drug effects/physiologyCell LineHippocampus/cytology/drug effects/metabolismHumansNeurons/drug effects/ metabolismNeuroprotective Agents/ pharmacologyOrgan Culture TechniquesPerfusionRats
PMID: 15851654
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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 https://archive-ouverte.unige.ch/unige:10371

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Deposited on : 2010-08-06

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