大鼠全脑缺血后海马CA1区锥体神经元L型钙通道电流的改变(英文)

Changes in Single L-Type Calcium Channel Currents in CA1 Pyramidal Neurons of Rat Hippocampus After Transient Forebrain Ischemia

已有研究表明在脑缺血期间及再灌流后早期,海马CA1锥体神经元细胞内钙浓度明显升高,这一钙超载被认为是缺血性脑损伤的重要机制之一.电压依赖性钙通道是介导正常CA1神经元钙内流的主要途径.实验观察了脑缺血再灌流后早期海马CA1锥体神经元电压依赖性L型钙通道的变化.以改良的四血管闭塞法制作大鼠 15min前脑缺血模型,在急性分离的海马CA1神经元上,采用膜片钳细胞贴附式记录L型电压依赖性钙通道电流.脑缺血后CA1神经元L型钙通道的总体平均电流明显增大,这是由于通道的开放概率增加所致.进一步分析单通道动力学显示,脑缺血后通道的开放时间变长,通道的开放频率增大.

It has been shown that intracellular Ca 2+ in hippocampal CA1 neurons is elevated during ischemia and at early period following reperfusion. This Ca 2+ overload has been suggested to be involved in ischemic brain damage. In normal CA1 neurons, the major mechanism allowing Ca 2+ entry from the extracellular compartment is the opening of voltage gated Ca 2+ channels. The aim of the present study was to explore whether L type calcium channel in hippocampal CA1 neurons changed at early period of reperfusion after ischemia. Transient forebrain ischemia in a duration of 15 min was induced by the use of the 4 vessel occlusion method in rats. Single L type calcium currents were recorded in cell attached patches of actually dissociated hippocampal CA1 neurons. After ischemia, average total patch current of L type Ca 2+ channels significantly increased in CA1 neurons when compared with that of control. This ischemia induced enhancement in channel function was due to a higher channel open probability. Further analysis of single channel kinetics showed a prolonged open time and an increased opening frequency in postischemic channels. It is suggested that the functional enhancement in L type calcium channels may partially account for the postischemic increase in intracellular Ca 2+ concentration of CA1 neurons following ischemia.