L-Type Ca 2+ Channel Blockers Attenuate Electrical Changes and Ca 2+ Rise Induced by Oxygen/Glucose Deprivation in Cortical Neurons

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Abstract
Background and Purpose—Experimental evidence supports a major role of increased intracellular calcium [Ca2+]i levels in the induction of neuronal damage during cerebral ischemia. However, the source of Ca2+ rise has not been fully elucidated. To clarify further the role and the origin of Ca2+ 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 [Ca2+]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 [Ca2+]i levels. When O2/glucose depri...