Abstract
IN mammalian cardiac cells, a variety of transient or sustained K+ currents contribute to the repolarization of action potentials1. There are two main components of the delayed-rectifier sustained K+ current, IKr (rapid) and IKS (slow)2. IKr is the product of the gene HERG3,4 which is altered in the long-QT syndrome, LQT2 (ref. 5). A channel with properties similar to those of the IKS channel is produced when the cardiac protein IsK is expressed in Xenopus oocytes6–8. However, it is a small protein with a very unusual structure for a cation channel9–15. The LQT1 gene is another gene associated with the LQT syndrome, a disorder that causes sudden death from ventricular arrhythmias16. Here we report the cloning of the full-length mouse KVLQT1 complemen-tary DNA and show that KVLQT1 associates with IsK to form the channel underlying the IKS cardiac current, which is a target of class-Ill anti-arrhythmic drugs and is involved in the LQT1 syndrome.
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References
Deal, K. K., England, S. K. & Tamkun, M. M. Physiol. Rev. 76, 49–67 (1996).
Sanguinetti, M. C. & Jurkiewicz, N. K. J. Gen. Physiol. 96, 195–215 (1990).
Sanguinetti, M. C., Jiang, C. G., Curran, M. E. & Keating, M. T. Cell 81, 299–307 (1995).
Trudeau, M. C., Warmke, J. W., Ganetzky, B. & Robertson, G. A. Science 269, 92–95 (1995).
Curran, M. E. et al. Cell 80, 795–803 (1995).
Takumi, T., Ohkubo, H. & Nakanishi, S. Science 242, 1042–1045 (1988).
Folander, K. et al. Proc. Natl Acad. Sci. USA 87, 2975–2979 (1990).
Honore, E. et al. EMBO J. 10, 2805–2811 (1991).
Attali, B. et al. Nature 365, 850–852 (1993).
Blumenthal, E. M. & Kaczmarek, L. K. J. Neurosci. 14, 3097–3105 (1994).
Freeman, L. C. & Kass, R. S. Circ. Res. 73, 968–973 (1993).
Hice, R. E. et al. Eur. J. Physiol. 426, 139–145 (1994).
Lesage, F. et al. Recept. Channels 1, 143–152 (1993).
Tzounopoulos, T., Guy, H. R., Durell, S., Adelman, J. P. & Maylie, J. Proc. Natl Acad. Sci. USA 92, 9593–9597 (1995).
Zhang, Z. J. et al. Proc. Natl Acad. Sci. USA 91, 1766–1770 (1994).
Wang, Q. et al. Nature Genet. 12, 17–23 (1996).
Nuss, H. B. & Marban, E. J. Physiol. (Lond.) 479, 265–279 (1994).
Honore, E., Attali, B., Lesage, F., Barhanin, J. & Lazdunski, M. Biochem. Biophys. Res. Commun. 184, 1135–1141 (1992).
Benefraim, I., Shai, Y. & Attali, B. J. Biol. Chem. 271, 8768–8771 (1996).
Attali, B. et al. J. Biol. Chem. 268, 24283–24289 (1993).
Lingueglia, E., Voilley, N., Waldmann, R., Lazdunski, M. & Barbry, P. FEBS Lett. 318, 95–99 (1993).
Guillemare, E. et al. Biochemistry 31, 12463–12468 (1992).
Hamill, O. P., Marty, A., Neher, E., Sakmann, B. & Sigworth, F. J. Pflugers Arch. 391, 85–100 (1981).
Fink, M. et al. J. Biol. Chem. 271, 26341–26348 (1996).
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Barhanin, J., Lesage, F., Guillemare, E. et al. KvLQT1 and IsK (minK) proteins associate to form the IKS cardiac potassium current. Nature 384, 78–80 (1996). https://doi.org/10.1038/384078a0
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DOI: https://doi.org/10.1038/384078a0
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