Gary V. Desir, M.D.

Professor of Medicine
Chief, VACHS Medical Service

B.A., 1976: New York University
M.D., 1980: Yale University
Residency: Yale-New Haven Hospital
Fellowship: Yale University

E-mail: gary.desir@yale.edu

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.

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References

Segal, AS., X. Yao, and GV. Desir. 2000. Structure-function relationships of Kv1.3: Interaction of the T0 domain with the pore region. J. Biol. Chem. 275:10859-10863.

Lang, R., G. Lee, W. Liu, S. Tian, H. Rafi, M. Orias, A. S. Segal, and G. V. Desir. 2000. KCNA10: a novel ion channel functionally related to both voltage-gated potassium and CNG cation channels. Am J Physiol Renal Physiol 278: F1013-21.

Yao, X., W. Liu, S. Tian, H. Rafi, A. S. Segal, and G. V. Desir. 2000. Close association of the N terminus of Kv1.3 with the pore region. J Biol Chem 275: 10859-63.

Velazquez, H., T. Silva, E. Andujar, G. V. Desir, D. H. Ellison, and R. Greger. 2001.The distal convoluted tubule of rabbit kidney does not express a functional sodium channel. Am J Physiol Renal Physiol 280: F530-9.

Tian, S., Liu, W., Rafi, H., and Desir, GV. 2002. Regulation of Kv channels by a new family of ?-subunits. (In Press, Am J Physiol Renal Physiol).

Desir, GV. MacAla, LJ., Rafi, H., Hayslett, JP. and Segal, AS. 2002. Verapamil inhibits EnaC and transepithelial sodium transport. (In Press, Am J Physiol Renal Physiol).

Jianchao Xu, Peili Wang, Pandelakis A. Koni, Richard A. Flavell, and Desir GV. 2002 Regulation of insulin sensitivity and body weight by the voltage-gated potassium channel Kv1.3 (Submitted).