Fahlke C, Rüdel R, Mitrovic N, Zhou M, George A L
Department of General Physiology, University of Ulm, Federal Republic of Germany.
Neuron. 1995 Aug;15(2):463-72. doi: 10.1016/0896-6273(95)90050-0.
A point mutation (D136G) predicting the substitution of glycine for aspartate in position 136 of the human muscle Cl- channel (hClC-1) causes recessive generalized myotonia. Heterologous expression of a recombinant D136G produces functional Cl- channels with profound alterations in voltage-dependent gating, without concomitant changes in pore properties. The mutant exhibits slowly activating current upon hyperpolarization, in contrast to wild-type channels, which display time-dependent current decay (deactivation) at negative membrane potentials. Steady-state activation of D136G depends upon the transmembrane Cl- gradient, reaching zero at voltages positive to the Cl- reversal potential in physiological Cl- distribution. This explains the reduced sarcolemmal Cl- conductance that causes myotonia. The functional disturbances exhibited by D136G may stem from a defect in the ClC-1 voltage sensor.
一种点突变（D136G），预测人类肌肉氯离子通道（hClC-1）第136位的天冬氨酸被甘氨酸取代，会导致隐性全身性肌强直。重组D136G的异源表达产生了功能性氯离子通道，其电压依赖性门控有深刻改变，而孔特性没有伴随变化。与野生型通道相反，突变体在超极化时表现出缓慢激活电流，野生型通道在负膜电位时显示时间依赖性电流衰减（失活）。D136G的稳态激活取决于跨膜氯离子梯度，在生理氯离子分布中，在高于氯离子反转电位的电压下达到零。这解释了导致肌强直的肌膜氯离子电导降低的原因。D136G表现出的功能紊乱可能源于ClC-1电压传感器的缺陷。
