Multiple modalities converge on a common gate to control K2P channel function |
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| Authors: | Sviatoslav N Bagriantsev R��mi Peyronnet Kimberly A Clark Eric Honor�� Daniel L Minor Jr |
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| Institution: | 1. Cardiovascular Research Institute, University of California, , San Francisco, CA, USA;2. Institut de Pharmacologie Moléculaire et Cellulaire, UMR CNRS, Université de Nice Sophia Antipolis, , Valbonne, France;3. Departments of Biochemistry and Biophysics, and Cellular and Molecular Pharmacology, University of California, , San Francisco, CA, USA;4. California Institute for Quantitative Biomedical Research, University of California, , San Francisco, CA, USA;5. Physical Biosciences Division, Lawrence Berkeley National Laboratory, , Berkeley, CA, USA |
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| Abstract: | 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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| Keywords: | K2P channel C‐type gate mechanical gating pH gating potassium channel temperature gating |
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