AN ASPARTIC-ACID RESIDUE IMPORTANT FOR VOLTAGE-DEPENDENT GATING OF HUMAN MUSCLE CHLORIDE CHANNELS

被引:98
作者
FAHLKE, C
RUDEL, R
MITROVIC, N
ZHOU, M
GEORGE, AL
机构
[1] VANDERBILT UNIV,MED CTR,DEPT PHARMACOL,NASHVILLE,TN 37232
[2] UNIV ULM,DEPT GEN PHYSIOL,D-89069 ULM,GERMANY
[3] UNIV ULM,DEPT APPL PHYSIOL,D-89069 ULM,GERMANY
关键词
D O I
10.1016/0896-6273(95)90050-0
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
A point mutation (D136G) predicting the substitution of glycine for aspartate in position 136 of the human muscle Cl- channel (hCIC-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 CIC-1 voltage sensor.
引用
收藏
页码:463 / 472
页数:10
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