Multiple modalities converge on a common gate to control K2P channel function.

Multiple modalities converge on a common gate to control K2P channel function.
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DOI:
10.1038/emboj.2011.230
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发表时间:
2011-07-15
期刊:
影响因子:
11.4
通讯作者:
Minor, Daniel L., Jr.
Minor, Daniel L., Jr.
中科院分区:
生物学1区
文献类型:
--
作者:
Bagriantsev, Sviatoslav N.;Peyronnet, Remi;Clark, Kimberly A.;Honore, Eric;Minor, Daniel L., Jr.

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Members of the K2P potassium channel family regulate neuronal excitability and are implicated in pain, anaesthetic responses, thermosensation, neuroprotection, and mood. Unlike other potassium channels, K2Ps are gated by remarkably diverse stimuli that include chemical, thermal, and mechanical modalities. It has remained unclear whether the various gating inputs act through separate or common channel elements. Here, we show that protons, heat, and pressure affect activity of the prototypical, polymodal K2P, K2P2.1 (KCNK2/TREK-1), at a common molecular gate that comprises elements of the pore-forming segments and the N-terminal end of the M4 transmembrane segment. We further demonstrate that the M4 gating element is conserved among K2Ps and is employed regardless of whether the gating stimuli are inhibitory or activating. Our results define a unique gating mechanism shared by K2P family members and suggest that their diverse sensory properties are achieved by coupling different molecular sensors to a conserved core gating apparatus.
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