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

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 ASICla channels are Ca 2+ permeable. Prior pharmacologic and genetic studies have shown that ASICla channel inactivation markedly diminishes CNS susceptibility to ischemic damage. Here, we characterize ASIC expression in oligodendrocyte lineage cells (OLQ by molecular, electrophysiological, calcium imaging, and immunofluorescence techniques. ASICla, ASIC2a, and ASIC4 mRNAs were expressed in cultured rat OLC, with steadystate 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 ASICla protein expression was detected in white matter oligodendroglia. Inactivating, proton-gated, amiloride-sensitive OLC currents were detected by wholecell voltage clamp. These currents showed profound tachyphylaxis with slow recovery, and were predominantly blocked by psalmotoxin, indicating that homomeric ASICla comprised a large fraction of functional ASIC in the cultured OLC. ASIC activation substantially dep6larized OLC plasma membrane in current clamp studies, and elicited transient elevations in intracellular Ca 21 in imaging studies. Thus, OLC ASICla 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. (c) 2008 Wiley-Liss, Inc.