RESTORATION OF INACTIVATION AND BLOCK OF OPEN SODIUM-CHANNELS BY AN INACTIVATION GATE PEPTIDE
RESTORATION OF INACTIVATION AND BLOCK OF OPEN SODIUM-CHANNELS BY AN INACTIVATION GATE PEPTIDE
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DOI：
10.1016/0896-6273(94)90312-3
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发表时间：
1994-05-01
期刊：
影响因子：
16.2
通讯作者：
CATTERALL, WA
中科院分区：
文献类型：
--
作者：
EAHOLTZ, G;SCHEUER, T;CATTERALL, WA
钠通道的失活终止了负责在可兴奋细胞中启动动作电位的钠电流。疏水序列（异亮氨酸-苯丙氨酸-甲硫氨酸，IFM）位于连接钠通道 α 亚基同源结构域 III 和 IV 的失活门片段中，是快速失活所必需的。含有 IFM 序列（乙酰基-KIFMK-酰胺）的合成肽可恢复失活门有缺陷的突变型钠通道和因 α-蝎毒素而减慢失活的野生型钠通道的快速失活。该肽还与内在失活颗粒竞争，并以电压和频率依赖性方式结合并阻断开放的钠通道。含有阻止快速失活的突变的肽（乙酰基-KIQMK-酰胺）不能有效恢复失活或阻断开放的钠通道。结果支持了序列IFM作为钠通道失活颗粒的假设，并表明它在失活过程中进入孔的细胞内口并堵塞它。
Inactivation of sodium channels terminates the sodium current responsible for initiation of action potentials in excitable cells. A hydrophobic sequence (isoleucine-phenylalanine-methionine, IFM), located in the inactivation gate segment connecting homologous domains III and IV of the sodium channel alpha subunit, is required for fast inactivation. A synthetic peptide containing the IFM sequence (acetyl-KIFMK-amide) restores fast inactivation to mutant sodium channels having a defective inactivation gate and to wild-type sodium channels having inactivation slowed by alpha-scorpion toxin. This peptide also competes with the intrinsic inactivation particle and binds to and blocks open sodium channels in a voltage- and frequency-dependent manner. A peptide (acetyl-KIQMK-amide) containing a mutation that prevents fast inactivation is not effective in restoring inactivation or in blocking open sodium channels. The results support the hypothesis that the sequence IFM serves as the inactivation particle of the sodium channel and suggest that it enters the intracellular mouth of the pore and occludes it during the process of inactivation.