title: Identification of a novel protein complex containing ASIC1a and GABAA receptors and their interregulation.
abstract: Acid-sensing ion channels (ASICs) belong to the family of the epithelial sodium channel/degenerin (ENaC/DEG) and are activated by extracellular protons. They are widely distributed within both the central and peripheral nervous systems. ASICs were modified by the activation of γ-aminobutyric acid receptors (GABAA), a ligand-gated chloride channels, in hippocampal neurons. In contrast, the activity of GABAA receptors were also modulated by extracellular pH. However so far, the mechanisms underlying this intermodulation remain obscure. We hypothesized that these two receptors-GABAA receptors and ASICs channels might form a novel protein complex and functionally interact with each other. In the study reported here, we found that ASICs were modified by the activation of GABAA receptors either in HEK293 cells following transient co-transfection of GABAA and ASIC1a or in primary cultured dorsal root ganglia (DRG) neurons. Conversely, activation of ASIC1a also modifies the GABAA receptor-channel kinetics. Immunoassays showed that both GABAA and ASIC1a proteins were co-immunoprecipitated mutually either in HEK293 cells co-transfected with GABAA and ASIC1a or in primary cultured DRG neurons. Our results indicate that putative GABAA and ASIC1a channels functionally interact with each other, possibly via an inter-molecular association by forming a novel protein complex.
authors.affiliation: Department of Thoracic Surgery, Shandong Cancer Hospital and Institute, Jinan, China.
authors.forename: Dongbo
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Department of Physiology, School of Medicine, Shandong University, Jinan, China.
authors.forename: Nannan
authors.initials: N
authors.lastname: Ning
authors.affiliation: Department of Anesthesiology, Qilu Hospital, Shandong University, Jinan, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Lei
authors.affiliation: Department of Thoracic Surgery, Shandong Cancer Hospital and Institute, Jinan, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Physiology, School of Medicine, Shandong University, Jinan, China.
authors.forename: Chuanfei
authors.initials: C
authors.lastname: Wei
authors.affiliation: Department of Physiology, School of Medicine, Shandong University, Jinan, China.
authors.forename: Dawei
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Physiology, School of Medicine, Shandong University, Jinan, China.
authors.forename: Jingxin
authors.initials: J
authors.lastname: Li
mesh_terms: D062565:Acid Sensing Ion Channels / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D003001:Cloning, Molecular; D005727:Ganglia, Spinal / Q000378:metabolism; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D009474:Neurons / Q000378:metabolism; D011485:Protein Binding / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000235:genetics* / Q000378:metabolism*; D014162:Transfection
chemical_list: C568266:ASIC1 protein, human; D062565:Acid Sensing Ion Channels; C546240:GABRA1 protein, human; C495710:GABRB2 protein, human; D011963:Receptors, GABA-A