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Upregulated GIRK2 Counteracts Ethanol-Induced Changes in Excitability and Respiration in Human Neurons.
Prytkova, Iya; Liu, Yiyuan; Fernando, Michael; Gameiro-Ros, Isabel; Popova, Dina; Kamarajan, Chella; Xuei, Xiaoling; Chorlian, David B; Edenberg, Howard J; Tischfield, Jay A; Porjesz, Bernice; Pang, Zhiping P; Hart, Ronald P; Goate, Alison; Slesinger, Paul A.
Afiliación
  • Prytkova I; Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York 10029.
  • Liu Y; Department of Genetics & Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029.
  • Fernando M; Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York 10029.
  • Gameiro-Ros I; Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York 10029.
  • Popova D; Human Genetics Institute, Rutgers University, Piscataway, New Jersey 08854.
  • Kamarajan C; Department of Psychiatry & Behavioral Sciences, SUNY Downstate Health Sciences University, Brooklyn, New York 11203.
  • Xuei X; Departments of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana 46202.
  • Chorlian DB; Department of Psychiatry & Behavioral Sciences, SUNY Downstate Health Sciences University, Brooklyn, New York 11203.
  • Edenberg HJ; Departments of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana 46202.
  • Tischfield JA; Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202.
  • Porjesz B; Human Genetics Institute, Rutgers University, Piscataway, New Jersey 08854.
  • Pang ZP; Department of Psychiatry & Behavioral Sciences, SUNY Downstate Health Sciences University, Brooklyn, New York 11203.
  • Hart RP; Human Genetics Institute, Rutgers University, Piscataway, New Jersey 08854.
  • Goate A; Department of Neuroscience and Cell Biology and The Child Health Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey 08901.
  • Slesinger PA; Human Genetics Institute, Rutgers University, Piscataway, New Jersey 08854.
J Neurosci ; 44(16)2024 Apr 17.
Article en En | MEDLINE | ID: mdl-38350999
ABSTRACT
Genome-wide association studies (GWAS) of electroencephalographic endophenotypes for alcohol use disorder (AUD) has identified noncoding polymorphisms within the KCNJ6 gene. KCNJ6 encodes GIRK2, a subunit of a G-protein-coupled inwardly rectifying potassium channel that regulates neuronal excitability. We studied the effect of upregulating KCNJ6 using an isogenic approach with human glutamatergic neurons derived from induced pluripotent stem cells (male and female donors). Using multielectrode arrays, population calcium imaging, single-cell patch-clamp electrophysiology, and mitochondrial stress tests, we find that elevated GIRK2 acts in concert with 7-21 d of ethanol exposure to inhibit neuronal activity, to counteract ethanol-induced increases in glutamate response, and to promote an increase intrinsic excitability. Furthermore, elevated GIRK2 prevented ethanol-induced changes in basal and activity-dependent mitochondrial respiration. These data support a role for GIRK2 in mitigating the effects of ethanol and a previously unknown connection to mitochondrial function in human glutamatergic neurons.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Etanol / Canales de Potasio Rectificados Internamente Asociados a la Proteína G Límite: Female / Humans / Male Idioma: En Revista: J Neurosci Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Etanol / Canales de Potasio Rectificados Internamente Asociados a la Proteína G Límite: Female / Humans / Male Idioma: En Revista: J Neurosci Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos