Conformational changes in CIC chloride transporters

National Institute Of Neurological Disorders And Stroke

Investigators

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Abstract

This project continued studying conformational changes in ClC-type chloride channel proteins. The ClC family of chloride-conducting ion channels is involved in a host of biological processes; these channels maintain the resting membrane potential in skeletal muscle, modulate excitability in central neurons, and are involved in the homeostasis of pH in a variety of intracellular compartments. Despite their physiological importance, the mechanisms by which these channels function are poorly understood. We are attempting to understand the functional properties of these proteins by examining several family members, including both eukaryotic and prokaryotic homologs. We are currently focusing our mechanistic efforts on the lysosomal CLC, ClC-7. We have used a recently published method to retarget ClC-7 from lysosomes to the plasma membrane and are studying its transport properties using electrophysiology. Our initial characterization, nearly ready for publication, examines the external pH dependence of the ClC-7 transporter and probes the relationship between the transport cycle in a novel form of gating observed in the CLC's. Finally, we are working to develop new methods to observe the actions of individual transporters or small groups of these molecules using methods of nanotechnology