L-TYPE CA2+ CHANNEL BLOCKERS ATTENUATE ELECTRICAL CHANGES AND CA2+ RISE INDUCED BY OXYGEN GLUCOSE DEPRIVATION IN CORTICAL-NEURONS/

Background and Purpose-Experimental evidence supports a major role of increased intracellular calcium [Ca2+](i) levels in the induction of n euronal damage during cerebral ischemia. However, the source oi Ca2+ r ise has trot been fully elucidated. To clarify further the role and ti le origin of Ca2+ in cerebral ischemia, we have studied the effects of various pharmacological agents in an in vitro model of oxygen (O-2)/g lucose deprivation. Methods-Pyramidal cortical neurons were intracellu larly recorded fi-om a slice preparation. Electrophysiological recordi ngs and microfluorometric measurements of [Ca2+](i) were performed sim ultaneously in slices perfused with a glucose-free physiological mediu m equilibrated with a 95% N-2/5% CO2 gas mixture. Results-Eight to twe lve minutes of O-2/glucose deprivation induced all initial membrane hy perpolarization, followed by a delayed, large but reversible membrane depolarization. The depolarization phase was accompanied by a transien t increase in [Ca2+](i) levels. When O-2/glucose deprivation exceeded 13 to 15 minutes, both membrane depolarization and [Ca2+](i) rise beca me irreversible, The dihydropyridines nifedipine and nimodipine signif icantly reduced either the membrane depolarization or the [Ca2+](i) el evation, In contrast, tetrodotoxin had no effect on either of these pa rameters. Likewise, antagonists of ionotropic and group I and II metab otropic glutamate receptors failed to reduce the depolarization of the cell membrane and the [Ca2+](i) accumulation. Finally, dantrolene, bl ocker of intracellular Ca2+ release, did not reduce both electrical an d [Ca2+](i) changes caused by O-2/glucose depletion. Conclusions-This work supports a role of L-type Ca2+ channels both in the electrical an d ionic changes occurring during the early phases of O-2/glucose depri vation.