Referenced in: none

Automatically associated channels: ClC1 , ClC4 , Slo1

Title: An aspartic acid residue important for voltage-dependent gating of human muscle chloride channels.

Authors: C Fahlke, R Rüdel, N Mitrovic, M Zhou, A L George

Journal, date & volume: Neuron, 1995 Aug , 15, 463-72

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/7646898

Abstract
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.