Molecular mechanisms of ion conduction in ClC-type chloride channels: lessons from disease-causing mutations.
The muscle Cl- channel, ClC-1, is a member of the ClC family of voltage-gated Cl- channels. Mutations in CLCN1, the gene encoding this channel, cause two forms of inherited human muscle disorders: recessive generalized myotonia congenita (Becker) and dominant myotonia (Thomsen). The functional characterization of these naturally occurring mutations not only allowed a better understanding of the pathophysiology of myotonia, it also provided important insights into the structure and function of the entire ClC channel family. This review describes recent experiments using a combination of cellular electrophysiology, molecular genetics, and recombinant DNA technology to study the molecular basis of ion permeation and selection in ClC-type chloride channels.
Fahlke
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Department of Pharmacology, Vanderbilt University, Nashville, Tennessee, USA. chfahlke@physiology.rwth-aachen.de
D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D000838:Anions / Q000378:metabolism; D018118:Chloride Channels / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D007477:Ions; D008954:Models, Biological; D009154:Mutation / Q000502:physiology
D000838:Anions; C086321:CLC-1 channel; D018118:Chloride Channels; D007477:Ions