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      Glutamate Permeability of Chicken Best1

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          Abstract

          Bestrophin-1 (Best1) is a calcium (Ca 2+)-activated chloride (Cl -) channel which has a phylogenetically conserved channel structure with an aperture and neck in the ion-conducting pathway. Mammalian mouse Best1 (mBest1) has been known to have a permeability for large organic anions including gluconate, glutamate, and D-serine, in addition to several small monovalent anions, such as Cl -, bromine (Br -), iodine (I -), and thiocyanate (SCN -). However, it is still unclear whether non-mammalian Best1 has a glutamate permeability through the ion-conducting pathway. Here, we report that chicken Best1 (cBest1) is permeable to glutamate in a Ca 2+-dependent manner. The molecular docking and molecular dynamics simulation showed a glutamate binding at the aperture and neck of cBest1 and a glutamate permeation through the ion-conducting pore, respectively. Moreover, through electrophysiological recordings, we calculated the permeability ratio of glutamate to Cl - (P Glutamate/P Cl) as 0.28 based on the reversal potential shift by ion substitution from Cl - to glutamate in the internal solution. Finally, we directly detected the Ca 2+-dependent glutamate release through cBest1 using the ultrasensitive two-cell sniffer patch technique. Our results propose that Best1 homologs from non-mammalian (cBest1) to mammalian (mBest1) have a conserved permeability for glutamate.

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                Author and article information

                Journal
                Exp Neurobiol
                Exp Neurobiol
                Experimental Neurobiology
                The Korean Society for Brain and Neural Sciences
                1226-2560
                2093-8144
                31 October 2022
                31 October 2022
                31 October 2022
                : 31
                : 5
                : 277-288
                Affiliations
                [1 ]KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul 02841, Korea
                [2 ]Center for Cognition and Sociality, Institute for Basic Science, Daejeon 34126, Korea
                [3 ]Brain Science Institute, Korea Institute of Science and Technology, Seoul 02792, Korea
                [4 ]IBS School, University of Science and Technology, Daejeon 34113, Korea
                [5 ]KIST School, University of Science and Technology, Seoul 02792, Korea
                Author notes
                [* ]To whom correspondence should be addressed. Ae Nim Pae, TEL: 82-2-958-5185, FAX: 82-2-958-6999, e-mail: anpae@ 123456kist.re.kr , C. Justin Lee, TEL: 82-42-878-9150, FAX: 82-42-878-9151, e-mail: cjl@ 123456ibs.re.kr
                [†]

                These authors contributed equally to this article.

                Article
                en-31-5-277
                10.5607/en22038
                9659495
                36351838
                f8a7d4ce-3114-460c-ba2b-0d9eafc738e2
                Copyright © Experimental Neurobiology 2022

                This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 16 October 2022
                : 28 October 2022
                : 28 October 2022
                Categories
                Short Communication

                Neurosciences
                chicken best1,glutamate permeability,molecular docking simulation,molecular dynamics simulation,whole-cell patch-clamp recording,two-cell sniffer patch

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