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(Stroke. 1998;29:196-202.)
© 1998 American Heart Association, Inc.

Original Contributions

L-Type Ca²⁺ Channel Blockers Attenuate Electrical Changes and Ca²⁺ Rise Induced by Oxygen/Glucose Deprivation in Cortical Neurons

Antonio Pisani, MD; Paolo Calabresi, MD; Alessandro Tozzi; Vincenza D'Angelo; Giorgio Bernardi, MD

From the Clinica Neurologica (A.P., P.C., A.T., V.D.), Dipartimento di Sanità, Università "Tor Vergata," and Ospedale S. Lucia, IRCCS, Rome, Italy.

Correspondence to Antonio Pisani, MD, Clinica Neurologica, Dipartimento di Sanità, Università "Tor Vergata," Via di Tor Vergata 135, 00133 Rome, Italy. E-mail pisani{at}utovrm.it

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 deprivation exceeded 13 to 15 minutes, both membrane depolarization and [Ca²⁺]_i rise became irreversible. The dihydropyridines nifedipine and nimodipine significantly reduced either the membrane depolarization or the [Ca²⁺]_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 [Ca²⁺]_i accumulation. Finally, dantrolene, blocker of intracellular Ca²⁺ release, did not reduce both electrical and [Ca²⁺]_i changes caused by O₂/glucose depletion.

Conclusions—This work supports a role of L-type Ca²⁺ channels both in the electrical and ionic changes occurring during the early phases of O₂/glucose deprivation.

Editorial Comment

Costantino Iadecola, MD, Guest Editor

Laboratory of Cerebrovascular Biology and Stroke, Department of Neurology, University of Minnesota, Minneapolis, Minnesota

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