The voltage-gated chloride channel, ClC-1, a member of the CLC family of proteins, is expressed predominantly in skeletal muscle cells. In this tissue, ClC-1 contributes to repolarisation and stabilisation of the membrane potential after an action potential. In the absence of ClC-1 function, voltage-gated sodium channels can recover from inactivation before the membrane potential has returned to resting levels, and hence can reopen without further stimulus, resulting in a run of contractions. Clinically, this phenomenon leads to the muscle stiffness disease myotonia. Members of the CLC family of proteins have been identified in many species from bacteria to mammals, and the X-ray crystallographic structure of a bacterial member of this family revealed a complex structure with 17 intramembrane helices. These proteins exist as a functional dimer, with a separate permeation pore within each subunit. There appears to be two separate gating mechanisms; the fast gate which acts on each pore independently and the slow or common gate operating on both pores simultaneously. The aim of this study was to identify functionally important regions within the ClC-1 channel, with the ultimate aim of elucidating the mechanisms involved in gating. / Thesis (PhDHealthSciences)--University of South Australia, 2006.
| Identifer | oai:union.ndltd.org:ADTP/267299 |
| Creators | Rickard, Heather Ruth. |
| Source Sets | Australiasian Digital Theses Program |
| Language | English |
| Detected Language | English |
| Rights | copyright under review |
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