L-Type Ca Channel Blockers Attenuate Electrical Changes and Ca Rise Induced by Oxygen/Glucose Deprivation in Cortical Neurons

Background and Purpose—Experimental evidence supports a major role of increased intracellular calcium [Ca]i levels in the induction of neuronal damage during cerebral ischemia. However, the source of Ca rise has not been fully elucidated. To clarify further the role and the origin of Ca in cerebral ischemia, we have studied the effects of various pharmacological agents in an in vitro model of oxygen (O2)/glucose deprivation. Methods—Pyramidal cortical neurons were intracellularly recorded from a slice preparation. Electrophysiological recordings and microfluorometric measurements of [Ca]i were performed simultaneously in slices perfused with a glucose-free physiological medium equilibrated with a 95% N2/5% CO2 gas mixture. Results—Eight to twelve minutes of O2/glucose deprivation induced an initial membrane hyperpolarization, followed by a delayed, large but reversible membrane depolarization. The depolarization phase was accompanied by a transient increase in [Ca]i levels. When O2/glucose deprivation exceeded 13 to 15 minutes, both membrane depolarization and [Ca ]i rise became irreversible. The dihydropyridines nifedipine and nimodipine significantly reduced either the membrane depolarization or the [Ca]i elevation. In contrast, tetrodotoxin had no effect on either of these parameters. Likewise, antagonists of ionotropic and group I and II metabotropic glutamate receptors failed to reduce the depolarization of the cell membrane and the [Ca]i accumulation. Finally, dantrolene, blocker of intracellular Ca 21 release, did not reduce both electrical and [Ca]i changes caused by O2/glucose depletion. Conclusions—This work supports a role of L-type Ca channels both in the electrical and ionic changes occurring during the early phases of O2/glucose deprivation. (Stroke. 1998;29:196-202.)