Ming Li, Ph.D.

Long-term interests of this laboratory are focused on the role of voltage-gated calcium channels in cellular excitability and hormone secretion. We have used pancreatic isleislet beng multiple types of voltage-gated calcium channels as a model system. Voltage-gated calcium channels are multi-subunit proteins with homologous principle subunits that are associated with multiple auxiliary subunits. The principal subunits are about 2500 amino acids in length and contain four homologous domains having six transmembrane segments in each. We are the first laboratory to isolate and clone the gene encoding the T-type calcium channel in pancreatic islet beta cells. We have demonstrated that this channel plays an important role in beta cell excitability and in the regulation of calcium homeostasis of the cell. We are also interested in developing new drugs that target calcium channels, which could be useful in the treatment of diabetes and other diseases. Techniques used in this laboratory include patch clamp recording, double electrode-voltage clamp, calcium fluorescence measuring, in combination with heterologous expression of cloned channels in mammalian cells and xenopus oocytes.

Publications

M. Li, J.D. McCann, C.M. Liedtke, A.C. Nairn, P. Greengard and M.J. Welsh: cAMP-dependent protein kinase opens chloride channels in normal but not cystic fibrosis airway epithelium. Nature 331:358-360. 1988.

D.C. Gruenert, C.B. Basbaun, M.J. Welsh, M. Li, W.E. Finkbeiner, and J.A. Nadel: Characterization of human tracheal epithelial cells transformed by an origin-defective simian virus 40. Proc. Natl. Acad. Sci. USA. 85: 5951-5955, 1988.

M. Li, J.D. McCann, M.P. Anderson, J.P. Clancy, C.M. Liedtke, A.C. Nairn, P. Greengard, and M.J.Welsh: Protein kinase C regulation of chloride channels in normal and cystic fibrosis airway epithelia. Science 244:1353-1356, 1989

J.D. McCann, M. Li, A.C. Nairn, P. Greengard, and M.J. Welsh: Identification and regulation of whole-cell chloride current in human tracheal epithelium. J. Gen. Physiol., 94:1015-1036, 1989.

J.P. Clancy, J.D. McCann, M. Li, and M.J. Welsh: Calcium-dependent regulation of airway epithelial chloride channels. Am J. Physiol: Lung Cellular and Molecular Physiol. 258:L25-L32, 1990.

M.J. Welsh, M. Li, and J.D. McCann: Activation of normal and cystic fibrosis chloride channels by voltage, temperature, and trypsin. J Clinic Invest. 84: 2002-2007, 1989.

M. Li: The regulation of apical chloride channels in airway epithelium. Ph.D. Dissertation, University of Iowa, 1989.

M.J. Welsh, M. Li, J.D. McCann, J.P. Clancy and M.P. Anderson: Phosphorylation-dependent regulation of apical membrane chloride channels in normal and cystic fibrosis airway epithelium. Annuls of the New York Academy of Sciences. 574:44-511989.

M. Li, J.D. McCann and M.J. Welsh: Apical membrane Cl channel in airway epithelia: anion selectivity and block by NPPB. Am J. Physiol.: Cell Physiol. 259 : C295-C301, 1990.

D.M. Jefferson, J.D. Valentich, F.C. Marini, S.A. Grubman, M.C. Lannazzi, H.L. Dorkin, M. Li, K.W. Klinger, M.J. Welsh: Expression of normal and cystic fibrosis phenotypes by continuous airway epithelial cell lines. Am J. Physiol.: Cell Physiol. 259 : L496-505, 1990.

M. Li, J. West, Y. Lai, T. Scheuer, W.A. Catterall: Functional Modulation of Brain Sodium channels by cAMP-dependent Phosphorylation. Neuron. 8: 1151-1159, 1992.

W.A. Catterall, T. Scheuer, R. Numann, M Li, J. West, B.J. Murphy, S. Rossie: Structure and modulation of voltage-gated sodium channels. NATO ASI Series: H60: 209-219, 1992.

M. Li, J. W. West, R. Numann, B.J. Murphy, T. Scheuer, W.A. Catterall: Convergent regulation of sodium channels by protein kinase C and cAMP-dependent protein kinase. Science 261:1439-1442, 1993

J.Y. Ma, M. Li, W.A. Catterall, T. Scheuer: Modulation of brain Na channels by a G protein-coupled pathway. Proc. Natl. Acad. Sci. USA. 91:12351-355, 1994

L. Wang, A. Bhattacharjee, J. Fu, M. Li: Abnormally expressed LVA calcium channels in b-cells from NOD mouse and a related clonal cell line. Diabetes 46:1678-1683, 1996.

J. Fu, J.G. Scammell, M. Li: Epidermal growth factor reduces L-type voltage-activated calcium current density in rat pituitary cells. Neuroendocrinology. 65:157-163, 1997.

A. Bhattacharjee, R.M. Whitehurst Jr., M. Zhang, L. Wang, M. Li: T-type calcium channels facilitate insulin secretion by enhancing general excitability in the insulin secreting cell line, INS-1. Endocrinology. 138 (9)3735-3740: 1997

T. M. Moore, G. H. Brough, P. Babal, J. Kelly, M. Li, T. Stevens: Activation of store-operated calcium entry promotes cell shape change in pulmonary endothelial cells expressing hTrp1. Am J Physiology 275:L574-L582, 1998

L. Wang, F. Hu, A. Bhattacharjee, Z. Zuo, R.E. Honkanen, P-O. Berggren, M. Li: A low-voltage-activated Ca2+ current mediates cytokine-induced pancreatic b-cell death. Endocrinology. 140:1200-1204, 1999.

R.M. Whitehurst Jr., M. Zhang, A. Bhattacharjee, M. Li: Dexamethasone induced hypertrophy in rat neonatal cardiac myocytes involves an elevated L-type Ca2+ current. J. Mol. Cell. Cardiol. 31:1551-1558, 1999

S. Wu, A. Bhattacharjee, M. Zhang, L.Liu, M. Li: A metabolite of mebefradil inhibits L-type calcium currents in the pancreatic b-cells. J Pharm Exp Therap, 292:939-943, 2000

H. Zhuang, A. Bhattacharjee, F. Hu, M. Zhang, S. Wu, P-O. Berggren, M. Li: Cloning of a T-type Ca2+ channels isofrom from a rat pancreatic b-cell line. Diabetes, 49:59-64, 2000.

S. Wu, T. M. Moore, G.H. Brough, M. Chinckers, M. Li, T. Stevens "Cyclic nucleotide gated channels mediate membrane depolarization following activation of store operated calcium entry". J. Biol. Chem. 275:18887-18896, 2000

N. Norwood, T. M. Moore, D. A. Dean. R. Bhattacharjee, M. Li, T. Stevens: Store-operated calcium entry and increased endothelial cell permeability. Am J Physiol. 279:L815-L814, 2000

T. Goswami, A. Bhattacharjee, P. Babal, E.G. Moore, M.E., Courad, M. Li, J.M. Blackwell: Nramp I is a pH dependent, divalent cation antiporter. Biochemical J. Biochemical J. 354:511-519, 2001.

G. H. Brough,, S. Wu, D. Cioffi, T. M. Moor, M. Li, N. Dean, T. Stevens "Contribution of Endogenously expressed Trp-1 to a Ca2+ selective store operated calcium entry pathway" FESAB J In press.

Funding

• American Heart Association, Southern Affiliate, P.I. 20%, "Role of T-type calcium channel in high glucose induced ventricular myocyte proliferation", $120,000, 2001-2003
• NIH R01, Co-PI, 20%, Dr. Stevens, P.I., "Store operated Ca2+ entry: lung endothelial permeability", $1,200,052, 1999-2003
• NIH (DK50151) R29, (P.I.)(50%) "Role of LVA Ca2+ channelin pancreatic B-cell death". $510,607, 1997-2002