Krafte D S, Goldin A L, Auld V J, Dunn R J, Davidson N, Lester H A
Division of Biology, California Institute of Technology, Pasadena 91125.
J Gen Physiol. 1990 Oct;96(4):689-706. doi: 10.1085/jgp.96.4.689.
This study investigates the inactivation properties of Na channels expressed in Xenopus oocytes from two rat IIA Na channel cDNA clones differing by a single amino acid residue. Although the two cDNAs encode Na channels with substantially different activation properties (Auld, V. J., A. L. Goldin, D. S. Krafte, J. Marshall, J. M. Dunn, W. A. Catterall, H. A. Lester, N. Davidson, and R. J. Dunn. 1988. Neuron. 1:449-461), their inactivation properties resemble each other strongly but differ markedly from channels induced by poly(A+) rat brain RNA. Rat IIA currents inactivate more slowly, recover from inactivation more slowly, and display a steady-state voltage dependence that is shifted to more positive potentials. The macroscopic inactivation process for poly(A+) Na channels is defined by a single exponential time course; that for rat IIA channels displays two exponential components. At the single-channel level these differences in inactivation occur because rat IIA channels reopen several times during a depolarizing pulse; poly(A+) channels do not. Repetitive stimulation (greater than 1 Hz) produces a marked decrement in the rat IIA peak current and changes the waveform of the currents. When low molecular weight RNA is coinjected with rat IIA RNA, these inactivation properties are restored to those that characterize poly(A+) channels. Slow inactivation is similar for rat IIA and poly(A+) channels, however. The data suggest that activation and inactivation involve at least partially distinct regions of the channel protein.
本研究调查了非洲爪蟾卵母细胞中由两个仅相差一个氨基酸残基的大鼠IIA钠通道cDNA克隆所表达的钠通道的失活特性。尽管这两个cDNA编码的钠通道具有显著不同的激活特性（奥尔德，V. J.，A. L. 戈尔丁，D. S. 克拉夫特，J. 马歇尔，J. M. 邓恩，W. A. 卡特拉尔，H. A. 莱斯特，N. 戴维森，以及R. J. 邓恩。1988年。《神经元》。1:449 - 461），但它们的失活特性彼此非常相似，却与由聚腺苷酸加尾大鼠脑RNA诱导的通道明显不同。大鼠IIA电流的失活更慢，从失活状态恢复得更慢，并且表现出向更正电位偏移的稳态电压依赖性。聚腺苷酸加尾钠通道的宏观失活过程由单一指数时间进程定义；而大鼠IIA通道的失活过程呈现两个指数成分。在单通道水平上，这些失活差异的出现是因为大鼠IIA通道在去极化脉冲期间会重新开放几次；聚腺苷酸加尾通道则不会。重复刺激（大于1赫兹）会使大鼠IIA峰值电流显著减小，并改变电流波形。当低分子量RNA与大鼠IIA RNA共注射时，这些失活特性会恢复为聚腺苷酸加尾通道所特有的特性。不过，大鼠IIA通道和聚腺苷酸加尾通道的缓慢失活是相似的。数据表明，激活和失活至少部分涉及通道蛋白的不同区域。
