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EMBO J. 2011 Aug 5;30(17):3607-19. doi: 10.1038/emboj.2011.268.

The pore structure and gating mechanism of K2P channels.

Author information

1
Universitätsklinikum Jena, Institute of Physiology II, Jena, Germany.

Erratum in

  • EMBO J. 2011 Nov 2;30(21):4515. Erhlich, Gunter [corrected to Ehrlich, Gunter].

Abstract

Two-pore domain (K2P) potassium channels are important regulators of cellular electrical excitability. However, the structure of these channels and their gating mechanism, in particular the role of the bundle-crossing gate, are not well understood. Here, we report that quaternary ammonium (QA) ions bind with high-affinity deep within the pore of TREK-1 and have free access to their binding site before channel activation by intracellular pH or pressure. This demonstrates that, unlike most other K(+) channels, the bundle-crossing gate in this K2P channel is constitutively open. Furthermore, we used QA ions to probe the pore structure of TREK-1 by systematic scanning mutagenesis and comparison of these results with different possible structural models. This revealed that the TREK-1 pore most closely resembles the open-state structure of KvAP. We also found that mutations close to the selectivity filter and the nature of the permeant ion profoundly influence TREK-1 channel gating. These results demonstrate that the primary activation mechanisms in TREK-1 reside close to, or within the selectivity filter and do not involve gating at the cytoplasmic bundle crossing.

PMID:
21822218
PMCID:
PMC3181484
DOI:
10.1038/emboj.2011.268
[Indexed for MEDLINE]
Free PMC Article

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