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Cell. 2016 Feb 25;164(5):937-49. doi: 10.1016/j.cell.2016.02.002.

A Non-canonical Voltage-Sensing Mechanism Controls Gating in K2P K(+) Channels.

Author information

1
Institute of Physiology, Christian-Albrechts University, 24118 Kiel, Germany.
2
Computational Biomolecular Dynamics Group, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany; Leibniz-Institut für Molekulare Pharmakologie, 13125 Berlin, Germany.
3
Clarendon Laboratory, Department of Physics, University of Oxford, Oxford OX1 3PU, UK.
4
Computational Biomolecular Dynamics Group, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany.
5
Clarendon Laboratory, Department of Physics, University of Oxford, Oxford OX1 3PU, UK; OXION Initiative, University of Oxford, Oxford OX1 3PU, UK.
6
Institute of Physiology, Christian-Albrechts University, 24118 Kiel, Germany; Nanion Technologies GmbH, 80636 Munich, Germany.
7
Institute of Physiology, Christian-Albrechts University, 24118 Kiel, Germany. Electronic address: t.baukrowitz@physiologie.uni-kiel.de.

Abstract

Two-pore domain (K2P) K(+) channels are major regulators of excitability that endow cells with an outwardly rectifying background "leak" conductance. In some K2P channels, strong voltage-dependent activation has been observed, but the mechanism remains unresolved because they lack a canonical voltage-sensing domain. Here, we show voltage-dependent gating is common to most K2P channels and that this voltage sensitivity originates from the movement of three to four ions into the high electric field of an inactive selectivity filter. Overall, this ion-flux gating mechanism generates a one-way "check valve" within the filter because outward movement of K(+) induces filter opening, whereas inward movement promotes inactivation. Furthermore, many physiological stimuli switch off this flux gating mode to convert K2P channels into a leak conductance. These findings provide insight into the functional plasticity of a K(+)-selective filter and also refine our understanding of K2P channels and the mechanisms by which ion channels can sense voltage.

PMID:
26919430
PMCID:
PMC4771873
DOI:
10.1016/j.cell.2016.02.002
[Indexed for MEDLINE]
Free PMC Article

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