利多卡因对大鼠海马CA1区锥体神经元L-型Ca^2＋通道开放功能的影响

Effect of lidocaine on conductance of the L-type Ca^2＋ channel of hippocampal CA1 pyramidal neurons in rats

目的研究不同浓度利多卡因对大鼠海马CA1区锥体神经元L-型Ca^2＋通道开放功能的影响。方法成年SD大鼠,体重200～250 g,雌雄不拘。麻醉后迅速断头取脑,采用酶加机械分离的方法急性分离海马CA1区锥体神经元。配制利多卡因溶液,终浓度依次为2、4、8、16、32μg/ml。选取活力好的细胞,采用膜片钳细胞贴附模式单通道记录技术,依次记录L-型Ca^2＋通道在不同浓度利多卡因作用下单通道的开放时间,并计算开放概率,共观察和记录7个锥体神经元。结果利多卡因对大鼠海马CA1区锥体神经元L-型Ca^2＋单通道功能的影响呈浓度依赖性：与未加利多卡因比较,2和4μg/ml利多卡因对L-型Ca^2＋单通道的功能无明显影响,8和16μg/ml利多卡因使L-型Ca^2＋单通道开放时间延长,开放概率增加（P〈0.05）;32μg/ml利多卡因使L-型Ca^2＋单通道开放时间缩短,开放概率降低（P〈0.05）。结论2和4μg/ml利多卡因对大鼠海马CA1区锥体神经元L-型Ca^2＋单通道无明显影响;8和16μg/ml时有增强作用;32μg/ml时有抑制作用。

Objective To investigate the effect of different concentrations of lidocaine on opening and closing of L-type calcium channel of hippocampal CA1 pyramidal neurons in rats.Methods Adult SD rats weighing 200-250 g were anesthetized with chloral hydrate.The animals were decapitated and their brains were immediately removed.The hippecampal CA1 pyramidal neurons were acutely dissociated by a combination of mechanical and enzymatic means.Five concentrations of lidocaine（2,4,8,16,32μg/ml）were prepared.The standard cell-attached mode of patch clamp technique was used to record the duration of L-type calcium channel opening and to calculate open probability（NPo）in seven isolated neurons.The data obtained were analyzed using a computerized acquisition and storage system.Results Lidocaine affected the duration of the opening of L-type calcium channel of hippocampal CA1 pyramidal neurons in a concentration-dependent manner.Lidocaine 2 and 4μg/ml did not significantly affect the conductance of L-type calcium channel as compared with lidocaine 0μg/ml. Lidocaine 8 and 16μg/ml significantly prolonged the duration of L-type calcium channel opening and increased NPo.While lidocaine 32μg/ml significantly shortened the duration of the L-type calcium channel opening and decreased Npe（P〈0.05）.Conclusion Lidocaine 2 or 4μg/ml has no significant effect on the L-type calcium channel conductance;while lidocaine 8 or 16μg/ml enhances but lidocaine 32μg/ml inhibits opening of the L-type calcium channel.