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Dorothy A. Hanck, Ph.D.
Professor
Department of Medicine, Section of Cardiology
Committee on Neurobiology
Committee on Cell Physiology
Committee on Computational Neuroscience


Mechanisms of ion channel gating.

My laboratory provides an integrated environment of electrophysiological, molecular biological, and modelling facilities for the study of basic biophysics and physiology of ion channels in health and disease. My research focuses on cardiac ion channel biophysics, physiology, and pharmacology with the goal of identifying heart specific characteristics and their structural bases that can be used to direct rationale drug design. On-going projects target specifically the cardiac Na channel including its intrinsic kinetics, metabolic regulation by phosphorylation, and interaction with clinically used antiarthythmic drugs. In addition, complementary studies on other isoforms of this channel, as found in the nervous and endocrine system as well as studies of potassium and calcium channels are also supported. The use molecular biological techniques to investigate the structural basis of channel behavior is supported and encouraged. The laboratory provides a full range of electrophysiological techniques, including (a) whole cell voltage clamp, (b) single channel recording, and (c) gating current recording. These techniques can be combined to study native channels in acutely isolated single myocytes and in cultured cells. The structural bases of functional characteristics identified in native cells can be pursued in several expression systems, including Xenopus oocytes, transiently transfected mammalian cells, and stable cell lines for a variety of cloned channels. In addition to experimental work, the laboratory offers a wide variety of computer based graphics and modelling tools for quantitative analyses and opportunities to test theory with experimental data.

 


References

Benzinger, G.R., Drum, C.L., Chen, L.Q., Kallen, R.G., and Hanck , D.A. (1997) Differences in the binding sites of two site-3 sodium channel toxins. PflŸgers Archiv., 434:742-749.

 Millonas, M.M. and Hanck, D.A. (1998) Non-equilibrium response spectroscopy of voltage sensitive ion channel gating. Biophysical Journal, 74:210-230.

 Benzinger, G.R., Kyle, J.W., Blumenthal, K.M., and Hanck, D.A. (1998) A specific interaction between the cardiac sodium channel and site-3 toxin Anthopleurin B. Journal of Biol Chem, 273:80-84.

 Millonas, M.M. and Hanck , D.A. Nonequilibrium response spectroscopy and the molecular kinetics of proteins. Physical Review Letters, 80:401-404.

 Hanck, D.A., Makielski, J.C., and Sheets, M.F. Altered gating of lidocaine-bound cardiac Na channels. Circulation Research, In review.

 Kyle, J.W., T. Sadanaga, D.A. Hanck, G.S. Tonkovich and M.S. Sheets. The Na channel 1 subunit destabilizes the inactivated states(s). Biophysical Journal, 72:A261, 1997

 Benzinger, G.R. and D.A. Hanck. Isoform-specific differences in recovery kinetics of Anthopleura toxin-modified sodium channels. Biophysical Journal, 72:A362, 1997.

 



Last updated 8/3/06