Molecular Biology of Voltage-Gated K+Channels
Voltage-gated K+ (Kv) channels may be assembled from various subunits as homoor heteromultimers. The pore-forming α-subunits are integral membrane proteins, which express functional tetrameric Kv channels in heterologous expression systems. Three main families encoding Kv channel α-subunits have been detected related to the Drosophila genes Shaker and ether-a-go-go and the human KvLQT1 (KCNQ1) gene. Members of each family contribute to cardiac Kv channels and to cardiac action potential repolarization. Auxiliary subunits do not express functional Kv channels by themselves. They associate with α-subunits and may modulate Kv channel properties, including voltage dependence of activation and inactivation, deactivation, single-channel conductance, recovery from inactivation, and pharmacology. Auxiliary β-subunits have a structure which suggests that they may function as NADPH-dependent oxidoreductases. Whether this putative enzymatic activity is independent of the association of β-subunits with the pore-forming α-subunits is not known. Auxiliary γ-subunits are similar in sequence and topology to Shaker-related α-subunits but yield functional Kv channels only when coexpressed with certain α-subunits. In most cases, however, the exact subunit compositions of native Kv channels have not been elucidated. Therefore, it is still difficult to know which of the cloned Kv channels contribute to the different components of outward K+ current in cardiac myocytes. In only a few cases has the combination of human genetics, molecular biology, electrophysiology, and pharmacology provided a clear-cut identification of the a and auxiliary subunits that contribute to native K+ currents.
KeywordsAttenuation Glycine Cysteine NADPH Triad
Unable to display preview. Download preview PDF.
- Acker, H., 1998, Reactive oxygen intermediates as mediators for regulating ion channel activity, in: Oxygen Regulation of Ion Channels and Gene Expression (J.Lopez-Barneo and E. K. Weir, eds.), Futura, Armonk,N.Y. pp. 9–18.Google Scholar
- Chandy, K. G., and Gutman, G. A., 1995, Voltage-gated potassium channel genes, in: Handbook of Receptors and Channels: Ligand- and Voltage-Gated Ion Channels (R. A. North, ed.) CRC Press, Boca Raton,Florida, pp. 1–71.Google Scholar
- Giles, W. R., and Imaizumi, Y., 1988, Comparison of potassium currents in rabbit atrial and ventricular cells,J. Physiol. (London) 405:123–145.Google Scholar
- Hille, B., 1992, Ionic Channels of Excitable Membranes, 2nd ed., Sinauer Associates, Inc., Sunderland,Massachusetts.Google Scholar
- London, B., Jeron, A., Zhou, A., Buckett, P., Han, X., Mitchell, G. F., and Koren, G., 1998, Long QT and ventricular arrhythmias in transgenic mice expressing the N terminus and the first transmembrane segment of a voltage-gated potassium channel, Proc. Natl. Acad. Sci. U.S.A. 95:2926–2931.PubMedCrossRefGoogle Scholar
- Lopez-Barneo, J., Montoro, R., Ortega-Saenz, P., and Urena, J., 1998, Oxygen-regulated ion channels, in:Oxygen Regulation of Ion Channels and Gene Expression (J. Lopez-Barneo and E. K. Weir, eds.), Futura Press, Armonk, N.Y. pp. 127–144.Google Scholar
- Shimoni, Y., Severson, D., and Giles, W. R., 1992, Thyroid status and diabetes modulate regional differences in potassium currents in rat ventricle, J. Physiol. (London) 488:673–688.Google Scholar