EFFECTS OF CEREBRAL-ISCHEMIA ON N-METHYL-D-ASPARTATE AND DIHYDROPYRIDINE-SENSITIVE CALCIUM CURRENTS - AN ELECTROPHYSIOLOGICAL STUDY IN THE RAT HIPPOCAMPUS IN-SITU

Background and Purpose During cerebral ischemia, both promoting and li miting factors are present for activation of the N-methyl-D-aspartate (NMDA) receptor ion channel and the dihydropyridine (DHP)-sensitive Ca 2+ channels. We investigated the activity of these channels during isc hemia and reperfusion in the rat hippocampus in situ. Methods Reversib le ischemia was induced by bilateral ca rotid artery ligation. NMDA an d BAY K8644 were applied by iontophoresis or pneumatic ejection, and e xtracellular 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 produ ced by NMDA and BAY K8644 were reduced when ischemia depressed the evo ked activity more than 50%. They disappeared on total failure of synap tic transmission and recovered during reperfusion. When the evoked act ivity was depressed less than 50%, DC shifts were greater than their p reischemic values; however, BAY K8644-induced potentiation did not rea ch statistical significance. CA1 neurons were depolarized during ische mia. Conclusions These data suggest that ischemia severe enough to cau se transmission failure inactivates NMDA and DHP-sensitive Ca2+ curren ts. During less intense ischemia and reperfusion, NMDA and DHP-sensiti ve Ca2+ channels are functional, and their overactivation may lead to neurotoxicity.