title: Analysis of ischemic neuronal injury in Cav2.1 channel α1 subunit mutant mice.
abstract: One of the main instigators leading to cell death and brain damage following ischemia is Ca(2+) dysregulation. Neuronal membrane depolarization results in the activation of voltage-gated Ca(2+) (CaV) channels and intracellular Ca(2+) influx. We investigated the physiological role of the CaV2.1 (P/Q-type) channel in ischemic neuronal injury using CaV2.1 channel α1 subunit mutant mice, rolling Nagoya and leaner mice. The in vivo ischemia model with a complete occlusion of the middle cerebral artery showed that the infarct area at 24h was significantly smaller in rolling Nagoya (27.1±3.5% of total brain volume) and leaner (20.1±3.5%) mice compared to wild-type (42.9±4.5%) mice. In an in vitro Ca(2+) imaging study, oxygen-glucose deprivation using a hippocampal slice induced a significantly slower rate of increase in intracellular Ca(2+) concentration ([Ca(2+)]i) in rolling Nagoya (0.083±0.007/min) and leaner (0.062±0.006/min) mice compared to wild-type (0.105±0.008/min) mice. These results demonstrate that the mutant CaV2.1 channel in rolling Nagoya and leaner mice plays a different protective role in a ([Ca(2+)]i)-dependent manner in ischemic models and indicate that CaV2.1 channel blockers may be used preventively against ischemic injury.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095-1690, USA.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Tian
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhou
authors.forename: Linghan
authors.initials: L
authors.lastname: Gao
authors.forename: Guang
authors.initials: G
authors.lastname: He
authors.forename: Weizhong
authors.initials: W
authors.lastname: Jiang
authors.forename: Weidong
authors.initials: W
authors.lastname: Li
authors.forename: Eiki
authors.initials: E
authors.lastname: Takahashi
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020864:Calcium Channels, N-Type / Q000235:genetics* / Q000502:physiology; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D021122:Protein Subunits / Q000235:genetics / Q000502:physiology
chemical_list: D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D021122:Protein Subunits