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  A non-canonical voltage sensor controls gating in K2P K2 channels.

Schewe, M., Nematian-Ardestani, E., Sun, H., Musinszki, M., Cordeiro, S., Bucci, G., et al. (2016). A non-canonical voltage sensor controls gating in K2P K2 channels. Cell, 164(5), 937-949. doi:10.1016/j.cell.2016.02.002.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0029-6CDE-D Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002C-824E-6
Genre: Journal Article

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 Creators:
Schewe, M., Author
Nematian-Ardestani, E., Author
Sun, H.1, Author              
Musinszki, M., Author
Cordeiro, S., Author
Bucci, G., Author
de Groot, B. L.2, Author              
Tucker, S. J., Author
Rapedius, M., Author
Baukrowitz, T., Author
Affiliations:
1Department of NMR based Structural Biology, MPI for biophysical chemistry, Max Planck Society, ou_578567              
2Research Group of Computational Biomolecular Dynamics, MPI for biophysical chemistry, Max Planck Society, ou_578573              

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 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 oneway "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.

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Language(s): eng - English
 Dates: 2016-02-25
 Publication Status: Published in print
 Pages: -
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 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1016/j.cell.2016.02.002
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Title: Cell
Source Genre: Journal
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Pages: - Volume / Issue: 164 (5) Sequence Number: - Start / End Page: 937 - 949 Identifier: -