The properties of voltage-sensitive chloride channels / 한양의대학술지

ABSTRACT

Chloride (Cl) channels are probably found in every cell, from bacteria to mammals. Cl channels are distributed both in the plasma membrane and in intracellular organelles. Three well established structural classes of plasma membrane chloride channels now exist: the ligand-gated chloride channels, the cAMP-stimulated cystic fibrosis transmembrane conductance regulator channel, and the voltage-gated (or swelling-activated) members of the ClC chloride channel family. They have diverse functions, ranging from regulation of cell volume to transepithelial transport, homeostasis, and stabilization of membrane potential, signal transduction and acidification of intracellular organelles. These different functions require the presence of many distinct Cl channels, which are differentially expressed and regulated by various stimuli. A combination of mutagenesis and biophysical analysis has been used to correlate their structure with function. Also their physiological roles are explained by genetic defects leading to various inherited disease and knock-out mouse models. Thus, the loss of Cl channels leads to an impairment of transepithelial transport in Bartter's syndrome, to increased excitability in congenital myotonia, and to reduced endosomal acidification and impaired endocytosis in Dent's disease. Three major structural classes of chloride channels are known to date, but there may be others not yet identified at the molecular level. This review focuses on voltage-gated members of the ClC chloride channel family and their physiological roles.