胞内乳酸对急性分离大鼠新皮层神经元K_(ATP)通道的影响  

EFFECTS OF INTRACELLULAR LACTATE ON ATP SENSITIVE POTASSIUM CHANNELS IN ACUTELY DISSOCIATED CEREBRAL NEURONS OF RATS

作　　者：肖中举[1] 苏平[1] 高天明[1] 佟振清[1] 

机构地区：[1]第一军医大学生理学教研室,广州510515

出　　处：《中国神经科学杂志》1999年第4期263-267,共5页

基　　金：国家自然科学基金!(39570263);广东省自然科学基金!(950537)资助项目

摘　　要：采用膜片钳技术内面向外式记录法，研究了胞内乳酸对急性分离大鼠皮层神经元上ＡＴＰ敏感钾通道（ＫＡＴＰ通道）的影响。结果显示：浴槽液中加入５～２０ ｍ ｍ ｏｌ／Ｌ乳酸，通道电流幅度增大，电导由（２０２±１１）ｐＳ增到大（２５３±１３）ｐＳ；乳酸浓度＞ ２０ ｍ ｍ ｏｌ／Ｌ时，部分通道出现多级开放。当膜超极化时，乳酸可增加通道平均开放时间及开放概率并随其浓度的增大而增加。浴槽液中乳酸浓度为２０ ｍ ｍ ｏｌ／Ｌ时，ＡＴＰ阻断通道电流活动的半数有效浓度（ＩＣ５０）为１ ｍ ｍ ｏｌ／Ｌ，较无乳酸时ＩＣ５０（０．０５ ｍ ｍ ｏｌ／Ｌ）明显增高，即通道对ＡＴＰ敏感性明显降低（Ｐ＜ ０．０１）。上述结果表明：胞内乳酸可通过增大电导、增加开放概率、诱导多通道开放及降低通道的ＡＴＰ敏感性参与调节皮层神经元上ＫＡＴＰ通道。提示：脑在缺氧情况下，胞内无氧代谢所产生的乳酸可先于ＡＴＰ耗竭激活ＫＡＴＰ通道，降低神经元兴奋性，从而起到保护作用。By using inside out configuration of patch clamp technique,the effects of intracellular lactate on single ATP sensitive potassium channels were studied in acutely dissociated cerebral neurons of rats.Application of 5～20 mmol/L lactate into the bath solution remarkably increased the amplitude of single channel currents with a conductance increasing from (202±11)pS to (255±13)pS.Lactate beyond 20 mmol/L induced multiple channel openings in some patches.Lactate also increased the mean open times and open probabilities of single channels in a dose dependent fasion as the membrane potential held at hyperpolarization.When bath solution contained 20 mmol/L lactate,the inhibitory effect of ATP on channel open probabilities was significantly reduced,and IC 50 with and without lactate was 1 mmol/L and 0.05 mmol/L respectively.The present results demonstrate that intracellular lactate can modulate K ATP channel activities via increasing its conductance and open probability,inducing multiple channel openings and decreasing its sensitivity to ATP. It is suggested that the lactate produced by anaerobic metabolism during brain hypoxia may,prior to depletion of ATP,activate K ATP channels to suppress neural excitability and therefore protect neurons from hypoxic and ischemic insults.

关 键 词：乳酸 ATP敏感钾通道 皮层神经元 

分 类 号：R338.8[医药卫生—人体生理学]