Characteristics of protective effects of NMDA antagonist and calcium channel antagonist on ischemic calcium accumulation in rat hippocampal CA1 region.
Effects of excitatory amino acid receptor antagonists and voltage-dependent Ca(2+) channel antagonists on ischemia-induced intracellular free Ca(2+) accumulation in rat hippocampal slices were examined. Ischemia caused a large Ca(2+) accumulation in CA1 region but a small Ca(2+) accumulation in CA3 and dentate gyrus regions. When applied during ischemia, the NMDA receptor antagonist MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10-imine maleate) inhibited the ischemic Ca(2+) accumulation only in the CA1, but the non-NMDA receptor antagonist CNQX (6-cyano-7-nitroquinoxaline-2,3-dione) inhibited it in all the three regions. The L-type Ca(2+) channel antagonists nifedipine and verapamil inhibited the ischemic Ca(2+) accumulation only in the CA1 region, but omega-conotoxin, a N- and L-type Ca(2+) channel antagonist inhibited the Ca(2+) accumulation in all the three regions of the hippocampus. When applied after 5-min ischemia, nifedipine but not MK-801, inhibited sustained postiscehmic Ca(2+) elevation in the CA1 region but not in the CA3 and dentate gyrus regions. These findings suggest that the enhanced ischemia-induced Ca(2+) accumulation in the CA1 region is mediated via activation of both NMDA receptors and L-type-like Ca(2+) channels. It appears that sustained postischemic Ca(2+) elevation in the CA1 region is mediated via activation of L-type-like Ca(2+) channels, but not of NMDA receptors.
Kubo
T
T
Department of Pharmacology, Showa Pharmaceutical University, Machida, Tokyo, Japan.
Yokoi
T
T
Hagiwara
Y
Y
Fukumori
R
R
Goshima
Y
Y
Misu
Y
Y
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D018698:Glutamic Acid / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007511:Ischemia / Q000378:metabolism; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism
D002121:Calcium Channel Blockers; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D009543:Nifedipine; D002118:Calcium