Effects of cerebral ischemia on N-methyl-D-aspartate and dihydropyridine-sensitive calcium currents. An electrophysiological study in the rat hippocampus in situ.
OBJECTIVE
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.
Dalkara
T
T
Department of Neurology, Hacettepe University, Faculty of Medicine, Ankara, Turkey.
Ayata
C
C
Demirci
M
M
Erdemli
G
G
Onur
R
R
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D002120:Calcium Channel Agonists / Q000008:administration & dosage / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism*; D004095:Dihydropyridines / Q000008:administration & dosage / Q000494:pharmacology*; D017097:Electric Impedance; D004594:Electrophysiology; D005071:Evoked Potentials / Q000187:drug effects; D018690:Excitatory Amino Acid Agonists / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D007478:Iontophoresis; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism*; D015424:Reperfusion
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004095:Dihydropyridines; D018690:Excitatory Amino Acid Agonists; D007473:Ion Channels; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C038806:1,4-dihydropyridine