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Physiological functions of CLC Cl- channels gleaned from human genetic disease and mouse models

Item Type:Review
Title:Physiological functions of CLC Cl- channels gleaned from human genetic disease and mouse models
Creators Name:Jentsch, T.J., Poet, M., Fuhrmann, J.C. and Zdebik, A.A.
Abstract:The CLC gene family encodes nine different Cl() channels in mammals. These channels perform their functions in the plasma membrane or in intracellular organelles such as vesicles of the endosomal/lysosomal pathway or in synaptic vesicles. The elucidation of their cellular roles and their importance for the organism were greatly facilitated by mouse models and by human diseases caused by mutations in their respective genes. Human mutations in CLC channels are known to cause diseases as diverse as myotonia (muscle stiffness), Bartter syndrome (renal salt loss) with or without deafness, Dent's disease (proteinuria and kidney stones), osteopetrosis and neurodegeneration, and possibly epilepsy. Mouse models revealed blindness and infertility as further consequences of CLC gene disruptions. These phenotypes firmly established the roles CLC channels play in stabilizing the plasma membrane voltage in muscle and possibly in neurons, in the transport of salt and fluid across epithelia, in the acidification of endosomes and synaptic vesicles, and in the degradation of bone by osteoclasts.
Keywords:Anion Channels, Endocytosis, Transepithelial Transport, Volume Regulation, Cystic Fibrosis, Animals, Mice
Source:Annual Review of Physiology
Publisher:Annual Reviews
Page Range:779-807
Date:March 2005
Official Publication:https://doi.org/10.1146/annurev.physiol.67.032003.153245
PubMed:View item in PubMed

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