Calcium-calmodulin binding in ischemic rat neurons after calcium channel blocker therapy.
Calcium-calmodulin binding in ischemic rat neurons after calcium channel blocker therapy.
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DOI：
10.1161/01.str.21.6.948
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发表时间：
1990-06
期刊：
影响因子：
8.3
通讯作者：
J. C. Grotta;C. Picone;R. Earls;Randy Strong;L. Yao;J. R. Dedman
中科院分区：
文献类型：
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作者：
J. C. Grotta;C. Picone;R. Earls;Randy Strong;L. Yao;J. R. Dedman
钙通道阻滞剂如尼卡地平可改善全脑缺血后的结果，并可通过阻止钙内流和与钙调蛋白结合来减轻缺血性神经元损伤。我们跟踪了正常大鼠（n = 6）、未治疗的缺血大鼠（n = 15）和0.05 mg/kg/hr s.c.治疗的缺血大鼠中神经元钙-钙调素结合的时间和区域顺序。尼卡地平13例。在四血管闭塞30分钟后，将40微米的脑切片在对不与钙和脑蛋白结合的钙调蛋白特异性的抗钙调蛋白抗体中孵育。在缺血后立即和再灌注2小时和24小时后检查光显微镜切片。未结合的钙调素广泛染色可见于正常大鼠的所有海马区域和皮质。在未处理的缺血对照大鼠中，染色消失，表明所有区域在缺血后立即发生钙-钙调蛋白结合。然而，24小时后，皮质和齿状回的染色恢复正常，CA 1和CA 3的染色恢复最小。尼卡地平治疗的动物有显着减少钙-钙调素结合在CA 1和齿状回2小时后再灌注。这项研究表明，在临床相关剂量尼卡地平有一个有限的影响，钙-钙调蛋白结合在选择性脆弱的地区后，严重缺血。
Calcium channel blockers such as nicardipine improve outcome after global cerebral ischemia and may attenuate ischemic neuronal injury by preventing calcium influx and binding to calmodulin. We followed the temporal and regional sequence of neuronal calcium-calmodulin binding in normal rats (n = 6), untreated ischemic rats (n = 15), and ischemic rats treated with 0.05 mg/kg/hr s.c. nicardipine (n = 13). After 30 minutes of four-vessel occlusion, 40-microns brain sections were incubated in an anti-calmodulin antibody specific for calmodulin not bound to calcium and brain protein. Light-microscopic sections were examined immediately after ischemia and after 2 and 24 hours of reperfusion. Extensive staining of unbound calmodulin was seen in all hippocampal regions and in the cortex in normal rats. In untreated ischemic control rats, staining was lost, indicating calcium-calmodulin binding immediately after ischemia in all regions. However, after 24 hours, staining returned to normal in the cortex and dentate, and minimal staining returned in CA1 and CA3. Nicardipine-treated animals had significantly less calcium-calmodulin binding in CA1 and in the dentate after 2 hours of reperfusion. This study demonstrates that in clinically relevant doses nicardipine has a limited effect on calcium-calmodulin binding in selectively vulnerable regions after severe ischemia.