Alexander G. Obukhov, Ph.D.
Associate Professor of Cellular and Integrative Physiology
Cellular and Integrative Physiology Graduate Program
Ph.D.: Bogomoletz Institute of Physiology, Kiev, Ukraine (1988)
Postdoctoral Fellowship: Bogomoletz Institute of Physiology, Ukraine (1988-1992)
Humboldt Postdoctoral Fellowship: Free University, Berlin, Germany (1993-1994)
Regulation of TRP Channels in Neuroendocrine Cells.
My laboratory investigates the role of hormone-regulated calcium-permeable cation channels in chromaffin cells of the adrenal gland. Chromaffin cells release catecholamines in response to hypoglycemia and stress. It is known that calcium influx through voltage-gated calcium channels play a crucial role in mediating catecholamine release from chromaffin cells. Circulating hormones, such as angiotensin II and histamine, can also trigger secretion of catecholamines by activating calcium-permeable hormone-regulated cation channels in the plasma membrane of chromaffin cells. The molecular identity of the hormone-induced cation channels remain unknown in chromaffin cells.
TRPC (Canonical Transient Receptor Potential) channels form hormone-operated channels in the plasma membrane of many cell types. We hypothesize that TRPC channels are the molecular candidates for the endogenous hormone-operated cation channels in adrenal chromaffin cells. The main focus of our research is to study the biophysical properties and the function of TRPC channels in the adrenal gland. We presented evidence that TRPC4 and TRPC5 channels can provide sufficient Ca2+ influx to trigger a robust secretory response in voltage-clamped chromaffin cells. We cloned rat TRPC5 channel and demonstrated that the kinetics of the channel activation can be modulated by the scaffolding protein EBP50. Recently, we have demonstrated that, a cytosolic anionic residue, D633, mediates Mg2+ block and cation permeability of TRPC5. Other projects in the lab include investigation of the molecular determinants of cation selectivity of TRP channels in collaboration with Dr. Roger Hardie (Cambridge University, UK) and Dr. Craig Montell (The Johns Hopkins University School of Medicine).
Christakos S, Dhawan P, Peng X, Obukhov AG, Nowycky MC, Benn BS, Zhong Y, Liu Y, Shen Q. (2007) New insights into the function and regulation of vitamin D target proteins. J Steroid Biochem & Mol Biol 103: 405-410.
Liu CH, Wang T, Postma M, Obukhov AG, Montell C & Hardie RC. (2007) In vivo identification and manipulation of the Ca2+ selectivity filter in the Drosophila transient receptor potential channel. J. Neurosci. 27: 604-615.
Lee D, Obukhov AG, Shen Q, Liu Y, Dhawan P, Nowycky MC, Christakos S (2006) Calbindin-D28k decreases L-type calcium channel activity and modulates intracellular calcium homeostasis in response to K+ depolarization in a rat beta cell line RINr1046-38. Cell Calcium. 39: 475-485.
Obukhov AG, Nowycky MC (2005) A cytosolic residue mediates Mg2+ block and regulates inward current amplitude of a transient receptor potential channel. J Neurosci. 25:1234-1239.
Obukhov AG, Nowycky MC. (2004) TRPC5 activation kinetics are modulated by the scaffolding protein ezrin/radixin/moesin-binding phosphoprotein-50 (EBP50). J Cell Physiol. 201:227-235.
Obukhov AG, Nowycky MC (2002) TRPC4 can be activated by G-protein-coupled receptors and provides sufficient Ca(2+) to trigger exocytosis in neuroendocrine cells. J Biol Chem. 277:16172-16178.
Schaefer M, Plant TD, Obukhov AG, Hofmann T, Gudermann T, Schultz G (2000) Receptor-mediated regulation of the nonselective cation channels TRPC4 and TRPC5. J Biol Chem. 275:17517-17526.
Hofmann T, Obukhov AG, Schaefer M, Harteneck C, Gudermann T, Schultz G (1999) Direct activation of human TRPC6 and TRPC3 channels by diacylglycerol.Nature. 397:259-263.