Molecular mechanisms underlying membrane-potential-mediated regulation of neuronal K2P2.1 channels |
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| Authors: | Yifat Segal-Hayoun Asi Cohen Noam Zilberberg |
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| Institution: | 1. Division of Biology and Biological Engineering, California Institute of Technology, 1200 E California Blvd, Pasadena, CA 91125, USA;2. Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 E California Blvd, Pasadena, CA 91125, USA;3. Institut de Biochimie et Biophysique Moléculaire et Cellulaire (IBBMC), Unité Mixte de Recherche (UMR) 8619, CNRS, Université Paris-Sud, 91405 Orsay;4. Institute of Biology and Technology Saclay (iBitec-S), UMR 8221 Commissariat à l''Energie Atomique (CEA), CNRS, Université Paris-Sud and CEA Saclay, 91191 Gif sur Yvette, France;1. Epilepsie de l’enfant et plasticité cérébrale, INSERM U 663, Paris, France;2. Unité Fonctionnelle Neurométabolique, INSERM UMR S975, Institut du Cerveau et de la Moëlle Epinière, Paris, France;3. INSERM, U1099, Rennes F-35000, France;4. Laboratoire de Traitement du Signal et de l’Image (LTSI), Université de Rennes 1, Rennes F-35000, France;1. Wright State University, Department of Biological Sciences, 3640 Colonel Glenn Highway, Dayton, OH, 45435, USA;2. University of Missouri- Columbia, Division of Biological Sciences, 105 Tucker Hall, Columbia, MO, 65211-7400, USA |
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| Abstract: | The activity of background K2P channels adjusts the resting membrane potential to enable plasticity of excitable cells. Here we have studied the regulation of neuronal K2P2.1 (KCNK2, TREK-1) channel activity by resting membrane potential. When heterologously expressed, K2P2.1 currents gradually increased at hyperpolarizing potentials and declined at depolarizing potentials, with a midpoint potential of ? 60 mV. As K2P channels are not equipped with an integral voltage sensor, we sought extrinsic cellular components that could convert changes in the membrane electrical field to cellular activity that would indirectly modify K2P2.1 currents. We propose that membrane depolarization activated the Gq protein-coupled receptor pathway, in the apparent absence of ligand, resulting in phosphatidylinositol-4,5-bisphosphate (PIP2) depletion through the action of phospholipase C. Our results suggest a novel mechanism in which an indirect pathway confers membrane potential regulation onto channels that are not intrinsically voltage sensitive to enhance regulation of neuronal excitability levels. |
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