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 gat ed Cl- channels. Mutations in CLCN1. the gene encoding this channel, cause two forms of inherited human muscle disorders: recessive generalized myoton ia congenita (Becker) and dominant myotonia (Thomsen). The functional chara cterization of these naturally occurring mutations not only allowed a bette r understanding of the pathophysiology of myotonia, it also provided import ant insights into the structure and function of the entire ClC channel fami ly. This review describes recent experiments using a combination of cellula r electrophysiology molecular genetics. and recombinant DNA technology to s tudy the molecular basis of ion permeation and selection in ClC-type chlori de channels.