Analysis of ischemic neuronal injury in Ca(V)2.1 channel alpha(1) subunit mutant mice

作者：Tian, Xiaoli; Zhou, Ying; Gao, Linghan; He, Guang; Jiang, Weizhong; Li, Weidong; Takahashi, Eiki^*

来源：Biochemical and Biophysical Research Communications, 2013, 434(1): 60-64.

DOI：10.1016/j.bbrc.2013.03.066

• Ca(V)2.1
• Ca2 imaging
• Ischemic neuronal injury
• Leaner mice
• Middle cerebral artery occlusion
• Rolling Nagoya mice

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+ (Ca-V) channels and intracellular Ca2+ influx. We investigated the physiological role of the Ca(V)2.1 (P/Q-type) channel in ischemic neuronal injury using Ca(V)2.1 channel alpha(l) 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 24 h 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 Ca(V)2.1 channel in rolling Nagoya and leaner mice plays a different protective role in a ([Ca2+]i)l-dependent manner in ischemic models and indicate that Ca(V)2.1 channel blockers may be used preventively against ischemic injury.

• 出版日期2013-4-26
• 单位复旦大学; 上海交通大学