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

J Biol Chem

From the Department of Cellular and Molecular Physiology, Yale University, New Haven, Connecticut 06520-8026

Published: May 2014

AI Article Synopsis

  • Protons activate ASIC1a channels in the CNS, impacting brain function but understanding this role has been challenging.
  • A new optogenetic method was developed to control ASIC1a activation with light in brain slices and live animals.
  • The technique involves using a light-driven H(+) pump to acidify the environment and stimulate neuronal activity, offering a way to study ASIC1a's role in brain functions and animal behavior.

Article 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.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4140900PMC
http://dx.doi.org/10.1074/jbc.M114.550012DOI Listing

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