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A sensitive mechanism for cation modulation of potassium current

Nature Neuroscience volume 3, pages 429–430 (2000)Cite this article

Abstract

The human ether a go-go-related gene (HERG)1 encodes ion channels that produce IKr (ref. 2), a potassium current that drives repolarization in many excitable cells3,4,5. When the concentration of extracellular potassium ions ([K+]o) is raised, outward K+ current through HERG channels is paradoxically increased, despite a reduced electrochemical gradient2, but the molecular mechanism is not fully understood. Here we show that extracellular sodium ions potently blocked HERG current in K+o-free conditions, and that low [K+]o (<5 mM) in the physiological range opposed block by sodium; hence the fine tuning that extracellular K+ confers on IKr actually represents modulation of sodium block by potassium.

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Figure 1: HERG K+o augmentation is Na+o dependent.
Figure 2: HERG current is blocked by Na+o.

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Acknowledgements

We thank Louis DeFelice and Dan Roden for discussion and comments on the manuscript. This work was supported by National Institutes of Health (P01 HL46681) and an Established Investigator Award from the American Heart Association (J.R.B.).

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Authors and Affiliations

  1. Departments of Anesthesiology and Pharmacology, Vanderbilt University School of Medicine, Nashville, 37232, Tennessee, USA

    Hirotaka Numaguchi, J.P. Johnson Jr, Christina I. Petersen & Jeffrey R. Balser

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  1. Hirotaka Numaguchi
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  2. J.P. Johnson Jr
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  3. Christina I. Petersen
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  4. Jeffrey R. Balser
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Correspondence to Jeffrey R. Balser.

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Numaguchi, H., Johnson, J., Petersen, C. et al. A sensitive mechanism for cation modulation of potassium current. Nat Neurosci 3, 429–430 (2000). https://doi.org/10.1038/74793

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