title: A method for activation of endogenous acid-sensing ion channel 1a (ASIC1a) in the nervous system with high spatial and temporal precision.
abstract: Protons activate acid-sensing ion channel 1a (ASIC1a) in the central nervous system (CNS) although the impact of such activation on brain outputs remains elusive. Progress elucidating the functional roles of ASIC1a in the CNS has been hindered by technical difficulties of achieving acidification with spatial and temporal precision. We have implemented a method to control optically the opening of ASIC1a in brain slices and also in awake animals. The light-driven H(+) pump ArchT was expressed in astrocytes of mouse cortex by injection of adenoviral vectors containing a strong and astrocyte-specific promoter. Illumination with amber light acidified the surrounding interstitium and led to activation of endogenous ASIC1a channels and firing of action potentials in neurons localized in close proximity to ArchT-expressing astrocytes. We conclude that this optogenetic method offers a minimally invasive approach that enables examining the biological consequences of ASIC1a currents in any structure of the CNS and in the modulation of animal behaviors.
authors.affiliation: From the Department of Cellular and Molecular Physiology, Yale University, New Haven, Connecticut 06520-8026.
authors.forename: Tianbo
authors.initials: T
authors.lastname: Li
authors.affiliation: From the Department of Cellular and Molecular Physiology, Yale University, New Haven, Connecticut 06520-8026.
authors.forename: Youshan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: From the Department of Cellular and Molecular Physiology, Yale University, New Haven, Connecticut 06520-8026 cecilia.canessa@yale.edu.
authors.forename: Cecilia M
authors.initials: CM
authors.lastname: Canessa
mesh_terms: D062565:Acid Sensing Ion Channels / Q000502:physiology*; D000138:Acidosis / Q000503:physiopathology; D000143:Acids / Q000378:metabolism; D000200:Action Potentials / Q000502:physiology* / Q000528:radiation effects; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000502:physiology*; D016466:CHO Cells; D002450:Cell Communication / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D003412:Cricetulus; D006863:Hydrogen-Ion Concentration; D008027:Light; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D009924:Organ Culture Techniques; D010775:Photic Stimulation; D017494:Proton Pumps / Q000378:metabolism
chemical_list: C568267:ASIC1 protein, mouse; D062565:Acid Sensing Ion Channels; D000143:Acids; D017494:Proton Pumps
keywords: ASIC1a; Acidosis; ArchT; Astrocytes; Extracellular pH; Optogenetics; Proton Pumps; pH Regulation
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