Acid-sensing ion channels in acidosis-induced injury of human brain neurons

Minghua Li, Koichi Inoue, Deborah Branigan, Eric Kratzer, Jillian C. Hansen, Jeff W. Chen, Roger P. Simon, Zhi Gang Xiong

Research output: Contribution to journalArticle

52 Scopus citations

Abstract

Acidosis is a common feature of the human brain during ischemic stroke and is known to cause neuronal injury. However, the mechanism underlying acidosis-mediated injury of the human brain remains elusive. We show that a decrease in the extracellular pH evoked inward currents characteristic of acid-sensing ion channels (ASICs) and increased intracellular Ca 2 in cultured human cortical neurons. Acid-sensing ion channels in human cortical neurons show electrophysiological and pharmacological properties distinct from those in neurons of the rodent brain. Reverse transcriptase-PCR and western blot detected a high level of the ASIC1a subunit with little or no expression of other ASIC subunits. Treatment of human cortical neurons with acidic solution induced substantial cell injury, which was attenuated by the ASIC1a blockade. Thus, functional homomeric ASIC1a channels are predominantly expressed in neurons from the human brain. Activation of these channels has an important role in acidosis-mediated injury of human brain neurons.

Original languageEnglish (US)
Pages (from-to)1247-1260
Number of pages14
JournalJournal of Cerebral Blood Flow and Metabolism
Volume30
Issue number6
DOIs
StatePublished - Jun 1 2010

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Keywords

  • Acid-sensing ion channel
  • Brain injury
  • Human
  • Neuron
  • Patch clamp

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

Cite this

Li, M., Inoue, K., Branigan, D., Kratzer, E., Hansen, J. C., Chen, J. W., Simon, R. P., & Xiong, Z. G. (2010). Acid-sensing ion channels in acidosis-induced injury of human brain neurons. Journal of Cerebral Blood Flow and Metabolism, 30(6), 1247-1260. https://doi.org/10.1038/jcbfm.2010.30