Gary Vincent Desir MD
Professor of Medicine (Nephrology) and of Forestry And Environmental Studies; Associate Chair, Veteran Affairs
Role of the voltage-gated K channel, Kv1.3, in renal K secretion and glucose metabolism; mechanisms by which K channels regulate vascular tone
Current ProjectsUse of voltage-gated K channel-blocking compounds in treatment of type II diabetes; generation of a knock out mouse model to better understand KCNA10's function
We are currently examining the role of the voltage-gated K channel, Kv1.3, in renal K secretion and glucose metabolism. To that end, we used a knockout mouse for Kv1.3 (Koni et al, Compensatory anion currents in Kv1.3–channel–deficient thymocytes, Journal of Biological Chemistry 278:39443–39451 (2004)) and discovered that the channel in an important regulator of insulin sensitivity and skeletal muscle glucose uptake. We are now investigating the possibility that compounds that block the channels can be used to treat type II diabetes.
We also study the mechanisms by which K channels regulate vascular tone. The membrane potential of a vascular smooth muscle cell depolarizes during vasoconstriction and hyperpolarizes during vasodilatation. Membrane hyperpolarization is mediated in part by the opening of cGMP–activated K channels. We cloned a novel cyclic nucleotide gated K channel using a double–screening procedure based on the hypothesis these channels might share structural motifs with other K channels (particularly at the pore region) and also contain a cGMP–binding site similar to that present in previously characterized cGMP–binding proteins. The channel, KCNA10, is expressed in endothelial and vascular smooth muscle cells and its activity is regulated by cyclic nucleotides. We are generating a knock out mouse model to better understand KCNA10’s function.