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Journal of Biomedicine and Biotechnology
Volume 2011 (2011), Article ID 685328, 10 pages
http://dx.doi.org/10.1155/2011/685328
Review Article

Physiology and Pathophysiology of CLC-1: Mechanisms of a Chloride Channel Disease, Myotonia

1Department of Physiology, College of Medicine, National Taiwan University, Taipei 10051, Taiwan
2Center for Neuroscience and Department of Neurology, University of California, Davis, CA 95618, USA

Received 26 April 2011; Revised 18 July 2011; Accepted 10 September 2011

Academic Editor: Lars Larsson

Copyright © 2011 Chih-Yung Tang and Tsung-Yu Chen. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The CLC-1 chloride channel, a member of the CLC-channel/transporter family, plays important roles for the physiological functions of skeletal muscles. The opening of this chloride channel is voltage dependent and is also regulated by protons and chloride ions. Mutations of the gene encoding CLC-1 result in a genetic disease, myotonia congenita, which can be inherited as an autosmal dominant (Thomsen type) or an autosomal recessive (Becker type) pattern. These mutations are scattered throughout the entire protein sequence, and no clear relationship exists between the inheritance pattern of the mutation and the location of the mutation in the channel protein. The inheritance pattern of some but not all myotonia mutants can be explained by a working hypothesis that these mutations may exert a “dominant negative” effect on the gating function of the channel. However, other mutations may be due to different pathophysiological mechanisms, such as the defect of protein trafficking to membranes. Thus, the underlying mechanisms of myotonia are likely to be quite diverse, and elucidating the pathophysiology of myotonia mutations will require the understanding of multiple molecular/cellular mechanisms of CLC-1 channels in skeletal muscles, including molecular operation, protein synthesis, and membrane trafficking mechanisms.