Role of Ca(v) 2.3 (alpha1E ) Ca2+ channel in ischemic neuronal injury.
We investigated the role of the Ca(v)2.3 (alpha1E) channel in ischemic neuronal injury using Ca(v)2.3 mutant mice. In focal ischemia model with a complete occlusion of the middle cerebral artery in vivo, infarct at 24 h was significantly larger in Ca(v)2.3 mutant mice compared with that in wild-type controls. In vitro Ca2+ imaging studies using hippocampal slices revealed that oxygen-glucose deprivation induced a [Ca2+]i increase in the hippocampal CA1 region more vigorously in Ca(v)2.3 mutant mice than in wild-type controls, and that tetrodotoxin or bicuculline application abolished the difference between the genotypes. These results suggest that the Ca(v)2.3 channel plays a protective role in ischemic neuronal injury by a mechanism in which GABAergic neuronal actions are involved.
Toriyama
Hideyuki
H
Department of Pharmacology and Neurobiology, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, Japan.
Wang
Ling
L
Saegusa
Hironao
H
Zong
Shuqin
S
Osanai
Makoto
M
Murakoshi
Takayuki
T
Noda
Tetsuo
T
Ohno
Kikuo
K
Tanabe
Tsutomu
T
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics / Q000502:physiology*; D020908:Calcium Channels, R-Type; D027682:Cation Transport Proteins; D002544:Cerebral Infarction / Q000473:pathology; D018756:GABA Antagonists / Q000494:pharmacology; D005838:Genotype; D006624:Hippocampus / Q000378:metabolism; D066298:In Vitro Techniques; D051379:Mice; D008817:Mice, Mutant Strains / Q000235:genetics; D009420:Nervous System / Q000503:physiopathology; D026941:Sodium Channel Blockers; D013779:Tetrodotoxin / Q000494:pharmacology
C498916:Cacna1e protein, mouse; D015220:Calcium Channels; D020908:Calcium Channels, R-Type; D027682:Cation Transport Proteins; D018756:GABA Antagonists; D026941:Sodium Channel Blockers; D013779:Tetrodotoxin; D002118:Calcium; D001640:Bicuculline