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KCNK2: reversible conversion of a hippocampal potassium leak into a voltage-dependent channel

Nature Neuroscience volume 4, pages 486–491 (2001)Cite this article

Abstract

Potassium leak channels are essential to neurophysiological function. Leaks suppress excitability through maintenance of resting membrane potential below the threshold for action potential firing. Conversely, voltage-dependent potassium channels permit excitation because they do not interfere with rise to threshold, and they actively promote recovery and rapid re-firing. Previously attributed to distinct transport pathways, we demonstrate here that phosphorylation of single, native hippocampal and cloned KCNK2 potassium channels produces reversible interconversion between leak and voltage-dependent phenotypes. The findings reveal a pathway for dynamic regulation of excitability.

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Figure 1: Native KCNK2 leak pores are reversibly transformed into voltage-dependent channels by PKA-mediated phosphorylation.
Figure 2: Native and cloned KCNK2 channels show the same biophysical properties.
Figure 3: KCNK2 channels have a voltage-dependent phenotype when residue 348 is negatively charged via phosphorylation, mutation or modification.
Figure 4: Voltage-dependent activation of KCNK2 is not sensitive to potassium reversal potential or due to magnesium blockade.

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Acknowledgements

This work was supported by grants to S.A.N.G. from the National Institutes of Health. D.B. is supported by the Child Health Research Center (Yale University) and an award from the National Institute of Diabetes and Digestive and Kidney Diseases. We thank F. Sesti and R. Goldstein for discussions and advice during the course of this work.

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

    Detlef Bockenhauer, Noam Zilberberg & S. A. N. Goldstein

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Correspondence to S. A. N. Goldstein.

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Bockenhauer, D., Zilberberg, N. & Goldstein, S. KCNK2: reversible conversion of a hippocampal potassium leak into a voltage-dependent channel. Nat Neurosci 4, 486–491 (2001). https://doi.org/10.1038/87434

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