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J Biol Chem. 2014 May 30;289(22):15441-8. doi: 10.1074/jbc.M114.550012. Epub 2014 Apr 11.

A method for activation of endogenous acid-sensing ion channel 1a (ASIC1a) in the nervous system with high spatial and temporal precision.

Author information

1
From the Department of Cellular and Molecular Physiology, Yale University, New Haven, Connecticut 06520-8026.
2
From the Department of Cellular and Molecular Physiology, Yale University, New Haven, Connecticut 06520-8026 cecilia.canessa@yale.edu.

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.

KEYWORDS:

ASIC1a; Acidosis; ArchT; Astrocytes; Extracellular pH; Optogenetics; Proton Pumps; pH Regulation

PMID:
24727474
PMCID:
PMC4140900
DOI:
10.1074/jbc.M114.550012
[Indexed for MEDLINE]
Free PMC Article
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