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The conduction pore of a cardiac potassium channel

Nature volume 391, pages 605–608 (1998)Cite this article

Abstract

Ion channels form transmembrane water-filled pores that allow ions to cross membranes in a rapid and selective fashion. The amino acid residues that line these pores have been sought to reveal the mechanisms of ion conduction and selectivity1,2,3,4,5,6,7. The pore (P) loop8 is a stretch of residues that influences single-channel-current amplitude, selectivity among ions and open-channel blockade2,3,5 and is conserved in potassium-channel subunits previously recognized to contribute to pore formation5,9. To date, potassium-channel pores have been shown to form by symmetrical alignment of four P loops around a central conduction pathway10,11,12. Here we show that the selectivity-determining pore region of the voltage-gated potassium channel of human heart through which the IKs current passes includes the transmembrane segment of the non-P-loop protein minK. Two adjacent residues in this segment of minK are exposed in the pore on either side of a short barrier that restricts the movement of sodium, cadmium and zinc ions across the membrane. Thus, potassium-selective pores are not restricted to P loops or a strict P-loop geometry.

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Figure 1: Blockade of channels formed with rat minK by Cd2+.
Figure 2: Blockade by Cd2+ of channels formed with KvLQT1 alone or with human minK and KvLQT1.
Figure 3: Inhibition of G56C rat minK channels by external Cd2+ shows the hallmarks of pore blockade.
Figure 4: Inhibition of F57C rat minK channels by internal Zn2+ shows the hallmarks of pore blockade.

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Acknowledgements

We thank G. Abbott, B. Fakler, P. Ruppersberg and K. W. Wang for helpful discussions. The work was supported by a grant from the NIH-NIGMS to S.A.N.G. We also thank the late Dorothy W. Goldstein, to whom this paper is dedicated.

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  1. Departments of Pediatrics and Cellular and Molecular Physiology, Section of Developmental Biology and Biophysics, Boyer Center for Molecular Medicine, Yale University School of Medicine, 295 Congress Avenue, New Haven, 06536, Connecticut, USA

    Kwok-Keung Tai & Steve A. N. Goldstein

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Correspondence to Steve A. N. Goldstein.

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Tai, KK., Goldstein, S. The conduction pore of a cardiac potassium channel. Nature 391, 605–608 (1998). https://doi.org/10.1038/35416

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