Characterization of acid-sensing ion channel expression in oligodendrocyte-lineage cells

Daniel H. Feldman, Makoto Horiuchi, Krista Keachie, Erica Mccauley, Peter Bannerman, Aki Itoh, Takayuki Ito, David E Pleasure

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

Acid-sensing ion channels (ASICs) are widely expressed in neurons, where they serve in pain and mechanical sensation, and contribute to learning and memory. Six ASIC sub-unit proteins form homo- or heteromeric channel complexes with distinct physiological properties. Of such complexes, only monomeric ASIC1a channels are Ca 2+ permeable. Prior pharmacologic and genetic studies have shown that ASIC1a channel inactivation markedly diminishes CNS susceptibility to ischemic damage. Here, we characterize ASIC expression in oligodendrocyte lineage cells (OLC) by molecular, electrophysiological, calcium imaging, and immunofluorescence techniques. ASIC1a, ASIC2a, and ASIC4 mRNAs were expressed in cultured rat OLC, with steady-state levels of each of these mRNAs several-fold higher in oligodendroglial progenitors than in mature oligodendroglia. ASIC transcripts were also detected in brain white matter, and ASIC1a protein expression was detected in white matter oligodendroglia. Inactivating, proton-gated, amiloride-sensitive OLC currents were detected by whole-cell voltage clamp. These currents showed profound tachyphylaxis with slow recovery, and were predominantly blocked by psalmotoxin, indicating that homomeric ASIC1a comprised a large fraction of functional ASIC in the cultured OLC. ASIC activation substantially depolarized OLC plasma membrane in current clamp studies, and elicited transient elevations in intracellular Ca2+ in imaging studies. Thus, OLC ASIC1a channels provide a means by which an acid shift in CNS extracellular pH, by diminishing plasma membrane potential and increasing Ca2+ permeability, can activate OLC signaling pathways, and may contribute to OLC vulnerability to CNS ischemia.

Original languageEnglish (US)
Pages (from-to)1238-1249
Number of pages12
JournalGLIA
Volume56
Issue number11
DOIs
StatePublished - Aug 15 2008

Keywords

  • Inflammation
  • Intracellular calcium
  • Ischemia

ASJC Scopus subject areas

  • Immunology

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    Feldman, D. H., Horiuchi, M., Keachie, K., Mccauley, E., Bannerman, P., Itoh, A., Ito, T., & Pleasure, D. E. (2008). Characterization of acid-sensing ion channel expression in oligodendrocyte-lineage cells. GLIA, 56(11), 1238-1249. https://doi.org/10.1002/glia.20693