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.