Moorman J R, Kirsch G E, Brown A M, Joho R H
Department of Medicine, University of Texas Medical Branch, Galveston 77550.
Science. 1990 Nov 2;250(4981):688-91. doi: 10.1126/science.2173138.
Voltage-gated sodium channels are transmembrane proteins of approximately 2000 amino acids and consist of four homologous domains (I through IV). In current topographical models, domains III and IV are linked by a highly conserved cytoplasmic sequence of amino acids. Disruptions of the III-IV linker by cleavage or antibody binding slow inactivation, the depolarization-induced closed state characteristic of sodium channels. This linker might be the positively charged "ball" that is thought to cause inactivation by occluding the open channel. Therefore, groups of two or three contiguous lysines were neutralized or a glutamate was substituted for an arginine in the III-IV linker of type III rat brain sodium channels. In all cases, inactivation occurred more rapidly rather than more slowly, contrary to predictions. Furthermore, activation was delayed in the arginine to glutamate mutation. Hence, the III-IV linker does not simply act as a charged blocker of the channel but instead influences all aspects of sodium channel gating.
电压门控钠通道是由大约2000个氨基酸组成的跨膜蛋白，由四个同源结构域（I至IV）组成。在当前的拓扑模型中，结构域III和IV通过一段高度保守的氨基酸胞质序列相连。通过切割或抗体结合破坏III-IV连接子会减缓失活过程，失活是钠通道去极化诱导的关闭状态特征。这个连接子可能是带正电荷的“球”，被认为通过阻塞开放通道导致失活。因此，在III型大鼠脑钠通道的III-IV连接子中，将两个或三个相邻的赖氨酸基团中和，或者用谷氨酸替代精氨酸。在所有情况下，与预测相反，失活发生得更快而不是更慢。此外，精氨酸到谷氨酸的突变延迟了激活。因此，III-IV连接子不仅仅是通道的带电荷阻滞剂，而是影响钠通道门控的各个方面。
