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We examine different aspects of chloride channel function by asking two narrower questions.
1. What can we learn from ion channelopathies?
Mutations in the skeletal muscle chloride channel gene (CLCN-1) have been implicated in human diseases (myotonia congenita and recessive generalized myotonia) and in animal models of myotonia in mouse, goat, and dog. Myotonia is characterized by delayed relaxation of muscle secondary to sarcolemmal hyperexcitability. It is the result of diminished chloride conductance in the muscle cell membrane. These mutations are important links between the pathology of the disease and the basic physiology of skeletal muscle. We study the ClC-1 mutation in the myotonic goat using a combination of approaches. We want to further our understanding of structure-function relationships of the affected voltage-gated ion channels and of other skeletal muscle diseases.
2. What is the functional role of the CLCA proteins in the eye? The first member of the calcium-activated chloride channel family CLCA was cloned in 1995. Much less is known about this group of proteins. We cloned two new members of this family, mCLCA5 and mCLCA6. We used immunohistochemistry and in situ hybridization to localize mCLCA3 and mCLCA5 in the eye and are currently trying to identify the role for these channels in the eye.
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