Premium
Characterization of acid‐sensing ion channel expression in oligodendrocyte‐lineage cells
Author(s) -
Feldman Daniel H.,
Horiuchi Makoto,
Keachie Krista,
Mccauley Erica,
Bannerman Peter,
Itoh Aki,
Itoh Takayuki,
Pleasure David
Publication year - 2008
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.20693
Subject(s) - acid sensing ion channel , biology , microbiology and biotechnology , ion channel , homomeric , sodium channel , patch clamp , microglia , electrophysiology , biophysics , biochemistry , neuroscience , chemistry , protein subunit , inflammation , immunology , receptor , sodium , organic chemistry , gene
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 subunit 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 Ca 2+ 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 Ca 2+ permeability, can activate OLC signaling pathways, and may contribute to OLC vulnerability to CNS ischemia. © 2008 Wiley‐Liss, Inc.