The long-term objective of the Tamkun laboratory is to understand the regulation of muscle electrical excitability at both the cellular and molecular levels. Research in the lab revolves around five general themes:
(1) cloning of new ion channels from cardiac and vascular muscle,
(2) identification of channel domains involved in protein-protein interactions,
(3) examination of the signaling mechanisms/cellular processes that control ion channel function and tissue/cell-specific expression,
(4) characterization of mechanisms responsible for channel cell surface localization, and
(5) elucidation of the physiological role that a given channel plays within a particular tissue.

While the Tamkun group is best known for studying the cardiac action potential, the laboratory has expanded recently into studies of uterine smooth muscle ion channel expression. This second project is aimed at understanding uterine smooth muscle excitability and contraction at term. We have a poor understanding of the molecular mechanisms regulating uterine contraction. Therefore, increased knowledge of the ion channels that are up-regulated at term can only aid in the management of uterine dysfunctions such as premature labor.

Experimental systems employed range from heterologous expression systems for the functional analysis of cloned channel proteins to transgenic mice to examine the physiological role a particular channel may play. Representative questions include:
What component of the cardiac action potential is due to the cloned Kv1.5 K+ channel protein?
Why and how is the Kv1.5 K+ channel protein localized in heart to regions of myocyte contact?
What is the role of the Kv1.4 K+ channel in the function of vascular smooth muscle?
What controls the cell-specific mRNA splicing of K+ channel beta subunits?
Is Nav2 Na+ channel expression the rate limiting step in controlling myometrial contraction?
What are molecular mechanisms responsible for the up-regulation of Nav2 Na+ channel gene expression in late pregnancy uterus?

England, S.K., V.N. Uebele, H. Shear, J. Kodall, P.B. Bennett and M.M. Tamkun. (1995) Characterization of a K+ channel beta subunit expressed in human heart. Proc. Natl. Acad. Sci. USA 92:6309-6313.

England, S.K., V.N. Uebele, J. Kodali, P.B. Bennett and M.M. Tamkun. (1995) A novel K+ channel beta subunit (hKv beta1.3) is produced via alternative mRNA splicing. J. Biol. Chem. 270:28531-28534.

Uebele, V.N., S.K. England, S.W. Yeola, M.M. Tamkun and D.J. Snyders. (1996) Functional differences in Kv1.5 currents expressed in mammalian cell lines are due to the presence of endogenous Kv beta2.1 subunits. J. Biol. Chem. 271:2406-2412.

Knittle, T.J., K.L. Doyle and M.M. Tamkun. (1996) Immunolocalization of the mNAv2.3 Na+ channel in mouse heart: Up-regulation in myometrium during pregnancy. Am. J. Physiol. 270:C688-C696.

Deal, K.K., S.K. England and M.M. Tamkun. (1996) Molecular physiology of cardiac potassium channels. Physiol. Rev. 76:49-68.

Yeola, S.W., T.C. Rich, V.N. Uebele, M.M. Tamkun and D.J. Snyders. (1996) Molecular analysis of a binding site for quinidine in a human cardiac delayed rectifier K+ channel. Role of S6 in antiarrhythmic drug binding. Circ. Res. 78:1105-1114.

Mays, D.J., M.M. Tamkun and P.A. Boyden. (1997) The cell surface lozalization of the Kv1.5 K+ channel is altered in the epicardial border zone of infarcted canine ventricle. Cardiovasc. Pathobiol. 2:79-87.

Franqueza, L., M. Longobardo, J. Vicente, E. Delpon, M.M. Tamkun, J. Tamargo, D.J. Snyders and C. Valenzuela. (1997) Molecular determinants of stereoselecting bupivacaine block of Kv1.5 channels. Circ. Res. 81:1053-1064.

Martens, J.R., Kwak, Y.G., Tamkun, M.M. (1999) Modulation of Kv Channel a/b Subunit Interactions. Trends Cardiovascular Med.9, 253-258.

Martens, J.R., Navarro, R., Coppock, E.A., Nishiyama, A., Parshely, L., Grobaski, T.D., Tamkun, M.M. (2000) Differential targeting of Shaker-like K+ channels to lipid rafts. J. Biol. Chem. 275, 7443-7446.

Martens, J.R., Sakamoto, N., Sullivan, S.A., Grobaski, T.D., and Tamkun, M.M. (2001) Isoform specific targeting of Kv channels to distinct lipid raft populations. Kv1.5 targets to caveolae. J. Biol. Chem. 276, 8409-8414.

Nishiyama, A., Ishii, D.N., Backx, P.H.,Pulford, B.E., Birks, B.R., and Tamkun, M.M. (2001) Altered K+ channel gene expression, and protection against myosin heavy chain gene isotype switching by IGF-II, in diabetic rat ventricle. Amer. J. Physiol. 281, H1800-1807.

Coppock, E.A. and Tamkun, M.M. (2001) Differential expression of Kv channel alpha and beta subunits in the bovine pulmonary arterial circulation. Amer. J.Physiol. 281, L1350-1360.

Hulme, J.T. Martens, J.R., Navarro-Polanco, R., Nishiyama, A., and Tamkun, M.M. (2001) Voltage-gated K+ channels in the myocardium. In Potassium Channels in Cardiovascular Biology (Archer, S.L. and Rusch, N.J., eds.) Plenum Publishing, New York, pp 337-362.

Goldin, A.L., Barchi, R.L., Caldwell, J.H., Hofmann, F., Howe, J.R., Hunter, J.C., Kallen, R.G., Mandel, G., Meisler, M., Berwald-Netter, Y., Tamkun, M.M., Waxman, S.G., Wood, J.N., Catterall, W.A. (2001) Nomenclature of voltage-gated sodium channels. Neuron 28, 365-8.

Coppock, E.A., Martens, J.R., and Tamkun, M.M. (2001) Molecular basis of hypoxia-induced pulmonary vasoconstriction. Role of voltage-gated potassium channels. Amer. J. Physiol. 281:L1-L12.