PT - JOURNAL ARTICLE AU - Nikonenko, I. AU - Bancila, M. AU - Bloc, A. AU - Muller, D. AU - Bijlenga, P. TI - Inhibition of T-Type Calcium Channels Protects Neurons from Delayed Ischemia-Induced Damage AID - 10.1124/mol.104.010066 DP - 2005 Jul 01 TA - Molecular Pharmacology PG - 84--89 VI - 68 IP - 1 4099 - http://molpharm.aspetjournals.org/content/68/1/84.short 4100 - http://molpharm.aspetjournals.org/content/68/1/84.full SO - Mol Pharmacol2005 Jul 01; 68 AB - 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 CaV3.1 and CaV3.2 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.