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(Stroke. 1996;27:127-133.)
© 1996 American Heart Association, Inc.

Articles

Effects of Cerebral Ischemia on N-Methyl-D-Aspartate and Dihydropyridine-Sensitive Calcium Currents

An Electrophysiological Study in the Rat Hippocampus In Situ

Turgay Dalkara, MD, PhD; Cenk Ayata, MD; Mehmet Demirci, MD; Gül Erdemli, MD, PhD Rüstü Onur, MD, PhD

From the Departments of Neurology (T.D., M.D.) and Pharmacology (C.A., G.E., R.O.), Hacettepe University, Faculty of Medicine, Ankara, Turkey.

Correspondence to Turgay Dalkara, MD, PhD, Department of Neurology, Hacettepe University Hospital, Ankara, Turkey, TR 06100.

Background and Purpose During cerebral ischemia, both promoting and limiting factors are present for activation of the N-methyl-D-aspartate (NMDA) receptor ion channel and the dihydropyridine (DHP)-sensitive Ca²⁺ channels. We investigated the activity of these channels during ischemia and reperfusion in the rat hippocampus in situ.

Methods Reversible ischemia was induced by bilateral carotid artery ligation. NMDA and BAY K8644 were applied by iontophoresis or pneumatic ejection, and extracellular field potential and resistance changes were recorded from the CA1 region of the rat hippocampus. Resting membrane potentials of the CA1 neurons were also recorded.

Results DC potential shifts produced by NMDA and BAY K8644 were reduced when ischemia depressed the evoked activity more than 50%. They disappeared on total failure of synaptic transmission and recovered during reperfusion. When the evoked activity was depressed less than 50%, DC shifts were greater than their preischemic values; however, BAY K8644-induced potentiation did not reach statistical significance. CA1 neurons were depolarized during ischemia.

Conclusions These data suggest that ischemia severe enough to cause transmission failure inactivates NMDA and DHP-sensitive Ca²⁺ currents. During less intense ischemia and reperfusion, NMDA and DHP-sensitive Ca²⁺ channels are functional, and their overactivation may lead to neurotoxicity.

Key Words: calcium channels • cerebral ischemia • hippocampus • N-methyl-D-aspartate • rats

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