Concentration-jump analysis of voltage-dependent conductances activated by glutamate and kainate in neurons of the avian cochlear nucleus
Concentration-jump analysis of voltage-dependent conductances activated by glutamate and kainate in neurons of the avian cochlear nucleus
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DOI：
10.1016/s0006-3495(95)80057-3
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发表时间：
1995-11-01
影响因子：
3.4
通讯作者：
Trussell, LO
中科院分区：
文献类型：
--
作者：
Raman, IM;Trussell, LO
我们已经研究了从鸡的大细胞核中提取的电压钳夹的外部斑块和整个细胞中α -氨基-3-羟基-5-甲基-4-异恶唑丙酸受体电压敏感性的机制。对谷氨酸盐或盐的反应具有向外整流的电流-电压关系。在长时间暴露于激动剂中脱敏的速率和程度，以及短暂暴露于激动剂后失活的速率，在正电位下下降，表明动力学转变对膜电位敏感。当用阿尼西坦降低脱敏或用环噻嗪阻断脱敏时，峰值电导和失活动力学的电压依赖性仍然存在。此外，对谷氨酸脱敏的恢复速率不依赖于电压。当细胞外二价阳离子浓度降低时，盐酸盐诱发电流增加，但保持整流电压关系。在低盐浓度下，整流最强。令人惊讶的是，对谷氨酸脱敏反应或去盐后电流失活的非平稳方差分析显示，平均单通道电导增加，膜电位增加。这些数据表明，对高激动剂浓度的峰值响应的整流反映了通道电导的增加，而稳态电流的整流则由电压敏感的通道动力学主导。
We have examined the mechanisms underlying the voltage sensitivity of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors in voltage-clamped outside-out patches and whole cells taken from the nucleus magnocellularis of the chick. Responses to either glutamate or kainate had outwardly rectifying current-voltage relations. The rate and extent of desensitization during prolonged exposure to agonist, and the rate of deactivation after brief exposure to agonist, decreased at positive potentials, suggesting that a kinetic transition was sensitive to membrane potential. Voltage dependence of the peak conductance and of the deactivation kinetics persisted when desensitization was reduced with aniracetam or blocked with cyclothiazide. Furthermore, the rate of recovery from desensitization to glutamate was not voltage dependent. Upon reduction of extracellular divalent cation concentration, kainate-evoked currents increased but preserved rectifying current-voltage relations. Rectification was strongest at lower kainate concentrations. Surprisingly, nonstationary variance analysis of desensitizing responses to glutamate or of the current deactivation after kainate removal revealed an increase in the mean single-channel conductance with more positive membrane potentials. These data indicate that the rectification of the peak response to a high agonist concentration reflects an increase in channel conductance, whereas rectification of steady-state current is dominated by voltage-sensitive channel kinetics.