MICHAEL C. SANGUINETTI

Michael Sanguinetti

e-mail: sanguinetti@cvrti.utah.edu
Professor of Internal Medicine (Cardiology)

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:

Garg, V., Stary-Weinzinger, A., and Sanguinetti, M.C. (2013) ICA-105574 Interacts with a common binding site to elicit opposite effects on inactivation gating of EAG and ERG potassium channels. Molecular Pharmacology, 83(4):805-813.

Garg, V., Sachse, F.B., and Sanguinetti, M.C. (2012) Tuning of EAG K+ channel inactivation: molecular determinants of amplification by mutations and a small molecule. Journal of General Physiology, 140(3):307-324.

Garg, P., and Sanguinetti, M.C. (2012) Structure-activity relationship of fenamates as Slo2.1 channel activators. Molecular Pharmacology, 82(5):795-802.

Garg, V., Stary-Weinzinger, A., Sachse, F., and Sanguinetti, M.C. (2011) Molecular determinants for activation of human ERG1 potassium channels by 3-nitro-N-(4-phenoxyphenyl) benzamide. Molecular Pharmacology, 80(4):630-637.

Dai, L., Garg, V., and Sanguinetti, M.C. (2010) Activation of Slo2.1 channels by niflumic acid. Journal of General Physiology, 135:275-295.

Abbruzzese, J., Sachse, F., Tristani-Firouzi, M., and Sanguinetti, M.C. (2010) Modification of hERG1 channel gating by Cd2+. Journal of General Physiology, 136:203-224.

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.