Effects of cerebral ischemia on N-methyl-D-aspartate and dihydropyridine-sensitive calcium currents - An electrophysiological study in the rat hippocampus in situ
Effects of cerebral ischemia on N-methyl-D-aspartate and dihydropyridine-sensitive calcium currents - An electrophysiological study in the rat hippocampus in situ
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DOI：
10.1161/01.str.27.1.127
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发表时间：
1996-01-01
期刊：
影响因子：
8.3
通讯作者：
Onur, R
中科院分区：
文献类型：
--
作者：
Dalkara, T;Ayata, C;Onur, R
背景与目的脑缺血时，n -甲基- d -天冬氨酸（NMDA）受体离子通道和二氢吡啶（DHP）敏感的Ca2+通道的激活存在促进和限制因素。我们原位研究了这些通道在大鼠海马缺血和再灌注过程中的活性。方法双侧颈动脉结扎诱导可逆性缺血。NMDA和BAY K8644分别通过离子导入或气压射药作用于大鼠海马CA1区，记录细胞外场电位和电阻的变化。同时记录CA1神经元静息膜电位。结果NMDA和BAY K8644产生的直流电电位移位在缺血抑制50%以上时明显减少。它们在突触传递完全失败时消失，在再灌注时恢复。当诱发活动抑制小于50%时，脑直流电移大于缺血前值；然而，BAY k8644诱导的增强没有达到统计学意义。缺血时CA1神经元去极化。这些数据表明，缺血严重到足以导致传输失败，使NMDA和dhp敏感的Ca2+电流失活。在不太强烈的缺血和再灌注时，NMDA和dhp敏感的Ca2+通道是功能性的，它们的过度激活可能导致神经毒性。
Background and Purpose During cerebral ischemia, both promoting and limiting factors are present for activation of the N-methyl-D-aspartate (NMDA) receptor ion channel and the dihydropyridine (DHP)-sensitive Ca2+ channels. We investigated the activity of these channels during ischemia and reperfusion in the rat hippocampus in situ.Methods Reversible ischemia was induced by bilateral ca rotid artery ligation. NMDA and BAY K8644 were applied by iontophoresis or pneumatic ejection, and extracellular field potential and resistance changes were recorded from the CA1 region of the rat hippocampus. Resting membrane potentials of the CA1 neurons were also recorded.Results DC potential shifts produced by NMDA and BAY K8644 were reduced when ischemia depressed the evoked activity more than 50%. They disappeared on total failure of synaptic transmission and recovered during reperfusion. When the evoked activity was depressed less than 50%, DC shifts were greater than their preischemic values; however, BAY K8644-induced potentiation did not reach statistical significance. CA1 neurons were depolarized during ischemia.Conclusions These data suggest that ischemia severe enough to cause transmission failure inactivates NMDA and DHP-sensitive Ca2+ currents. During less intense ischemia and reperfusion, NMDA and DHP-sensitive Ca2+ channels are functional, and their overactivation may lead to neurotoxicity.