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Analysis of ischemic neuronal injury in CaV2.1 channel α1 subunit mutant mice

Author:
Tian, Xiaoli, Zhou, Ying, Gao, Linghan, He, Guang, Jiang, Weizhong, Li, Weidong, Takahashi, Eiki
Source:
Biochemical and biophysical research communications 2013 v.434 pp. 60-64
ISSN:
0006-291X
Subject:
brain, brain damage, calcium, image analysis, infarction, ischemia, mice, models, mutants, protective effect, rolling
Abstract:
One of the main instigators leading to cell death and brain damage following ischemia is Ca2+ dysregulation. Neuronal membrane depolarization results in the activation of voltage-gated Ca2+ (CaV) channels and intracellular Ca2+ 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 Ca2+ imaging study, oxygen–glucose deprivation using a hippocampal slice induced a significantly slower rate of increase in intracellular Ca2+ concentration ([Ca2+]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 ([Ca2+]i)-dependent manner in ischemic models and indicate that CaV2.1 channel blockers may be used preventively against ischemic injury.
Agid:
897347