Lee, Jung Moo Gadhe Changdev Gorakshnath Kang, Hyunji Pae, Ae Nim Lee, ChangJoon Justin 2024-01-12T02:36:19Z 2024-01-12T02:36:19Z 2022-11-22 2022-10 1226-2560 https://pubs.kist.re.kr/handle/201004/75977 Bestrophin-1 (Best1) is a calcium (Ca2+)-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 Ca2+-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- (PGlutamate/PCl) 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 Ca2+-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. English 한국뇌신경과학회 Glutamate Permeability of Chicken Best1 Article 10.5607/en22038 1 Experimental Neurobiology, v.31, no.5, pp.277 - 288 Experimental Neurobiology 31 5 277 288 N scie scopus kci 000903744000001 Medicine, Research & Experimental Neurosciences Research & Experimental Medicine Neurosciences & Neurology Article CL-CHANNELS DYNAMICS BESTROPHIN RELEASE GENE SIMULATIONS PROTEIN VMD2 Chicken Best1 Glutamate permeability Molecular docking simulation Molecular dynamics simulation Whole-cell patch-clamp recording Two-cell sniffer patch