MICHAEL C. SANGUINETTI
Michael C. Sanguinetti
email: sanguinetti@cvrti.utah.edu		 Professor of Physiology

The Sanguinetti Lab
Molecular Neuroscience
Neurobiology of Disease

B.S. 1976, Humboldt State University; M.S. 1978, San Jose State University; PhD. 1982, University of California, Davis; Postdoctoral Fellow, 1982-1984, University of Rochester.

RESEARCH:

Molecular mechanisms of ion channel gating, pharmacology and channelopathies

The Sanguinetti laboratory is interested in the structural basis of ion channel function. We use site-directed mutagenesis of cloned channels and voltage clamp techniques to study the molecular basis of hERG and Slo2.1 potassium channel gating and the molecular mechanisms and structural basis of action of ion channel blockers and activators. We also determine the perturbations in biophysical properties of hERG and KCNQ1 channels that result from mutations that cause several forms of inherited cardiac arrhythmia.

Selected Publications

Perry, M., Sachse, F., Abbruzzese, J., and Sanguinetti, M.C. (2009) PD-118057 contacts the pore helix of hERG1 channels to attenuate inactivation and enhance K+ conductance. Proceedings of the National Academy of Sciences, USA, (in press).

Cheng, L., and Sanguinetti, M.C. (2009) Niflumic acid alters gating of HCN2 pacemaker channels by interaction with the outer region of S4 voltage sensing domains. Molecular Pharmacology, 75(5):1210-1221.

Brown, S., Sonntag, D., and Sanguinetti, M.C. (2008) A highly conserved alanine in the S6 domain of the hERG1 K+ channel is required for normal gating. Cellular Physiology and Biochemistry, 22:601-610.

Decher, N., Gonzalez, T., Sachse, F.B., Renigunta, V., Kathrin Streit, A., Soom, M., Heineman, S.H., Daut, J., and Sanguinetti, M.C. (2008) Structural determinants of KvB1.3 induced channel inactivation: a hairpin modulated by PIP2. EMBO Journal, 27(23):3164-3174.

Restier, L., Cheng, L., and Sanguinetti, M.C. (2008) Mechanisms by which atrial fibrillation-associated mutations in the S1 domain of KCNQ1 slow deactivation of IKs channels. Journal of Physiology, 586:4179-4191.

Fernandez, D., Sargent, J., Sachse, F.B., and Sanguinetti, M.C. (2008) Structural basis for ether-a-go-go-related gene K+ channel subtype-dependent activation by niflumic acid. Molecular Pharmacology, 73:1159-1167.

Perry, M. and Sanguinetti, M.C. (2008) A single amino acid difference between ether-a-go-go-related gene channel subtypes determines differential sensitivity to a small molecule activator. Molecular Pharmacology, 73:1044-1051.

Perry, M., Sachse, F., and Sanguinetti, M.C. (2007) Structural basis of action for a human ether-a-go-go-related gene 1 potassium channel activator. Proceedings of the National Academy of Sciences, USA, 104:13827-13832.

Cheng, L., Kinard, K., Rajamani, R., and Sanguinetti, M.C. (2007) Molecular mapping of the binding site for a blocker of HCN2 pacemaker channels. Journal of Pharmacology and Experimental Therapeutics, 322(3):931-939.

Decher, N., Renigunta, V., Zuzarte, M., Soo, M., Heinemann, S.H., Daut, J., Timothy, K.W., Keating, M.T., Sanguinetti, M.C., and Splawski, I. (2007) Impaired interaction between the slide helix and the C-terminus of Kir2.1: a novel mechanism of Andersen syndrome. Cardiovascular Research, 75:748-757.

Antzelevitch, C., Pollevick, G.D., Cordeiro, J.M., Casis, O., Sanguinetti, M.C., et al. (2007) Loss-of-function mutations in the cardiac calcium channel underlie a new clinical entity characterized by ST-segment elevation, short QT intervals, and sudden cardiac death. Circulation, 115(4):442-449.

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