Characterization of acid-sensing ion channels in medium spiny neurons of mouse striatum

Neuroscience. 2009 Aug 4;162(1):55-66. doi: 10.1016/j.neuroscience.2009.04.029. Epub 2009 Apr 17.

Abstract

Acid-sensing ion channels (ASICs) regulate synaptic activities and play important roles in neurodegenerative diseases. They are highly expressed in the striatum, where medium spiny neurons (MSNs) are a major population. Given that the properties of ASICs in MSNs are unknown, in this study, we characterized ASICs in MSNs of the mouse striatum. A rapid drop in extracellular pH induced transient inward currents in all MSNs. The pH value for half-maximal activation was 6.25, close to that obtained in homomeric ASIC1a channels. Based on psalmotoxin 1 and zinc sensitivity, ASIC1a (70.5% of neurons) and heteromeric ASIC1a-2 channels (29.5% of neurons) appeared responsible for the acid-induced currents in MSNs. ASIC currents were diminished in MSNs from ASIC1, but not ASIC2, null mice. Furthermore, a drop in pH induced calcium influx by activating homomeric ASIC1a channels. Activation of ASICs increased the membrane excitability of MSNs and lowering extracellular Ca2+ potentiated ASIC currents. Our data suggest that the homomeric ASIC1a channel represents a majority of the ASIC isoform in MSNs. The potential function of ASICs in the striatum requires further investigation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acid Sensing Ion Channels
  • Action Potentials / physiology
  • Amiloride / administration & dosage
  • Animals
  • Calcium / metabolism
  • Cells, Cultured
  • Chlorides / administration & dosage
  • Corpus Striatum / cytology
  • Corpus Striatum / drug effects
  • Corpus Striatum / physiology*
  • Dose-Response Relationship, Drug
  • Extracellular Space / metabolism
  • Hydrogen-Ion Concentration
  • Intracellular Space / drug effects
  • Intracellular Space / metabolism
  • Membrane Potentials / physiology
  • Mice
  • Mice, Knockout
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neurons / drug effects
  • Neurons / physiology*
  • Peptides
  • Sodium Channel Blockers / administration & dosage
  • Sodium Channels / genetics
  • Sodium Channels / metabolism*
  • Spider Venoms / administration & dosage
  • Zinc Compounds / administration & dosage

Substances

  • ASIC1 protein, mouse
  • ASIC2 protein, mouse
  • Acid Sensing Ion Channels
  • Chlorides
  • Nerve Tissue Proteins
  • PcTX1 protein, Psalmopoeus cambridgei
  • Peptides
  • Sodium Channel Blockers
  • Sodium Channels
  • Spider Venoms
  • Zinc Compounds
  • Amiloride
  • zinc chloride
  • Calcium