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 ASIC1a channels are Ca2+ 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.
Feldman
Daniel H
DH
Institute for Pediatric Regenerative Medicine, Shriners Hospital for Children, Northern California, Sacramento, California 95817, USA. dhfeldman@ucdavis.edu
Horiuchi
Makoto
M
Keachie
Krista
K
Mccauley
Erica
E
Bannerman
Peter
P
Itoh
Aki
A
Itoh
Takayuki
T
Pleasure
David
D
D062565:Acid Sensing Ion Channels; D000818:Animals; D000831:Animals, Newborn; D019070:Cell Lineage / Q000502:physiology*; D002478:Cells, Cultured; D002490:Central Nervous System / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000096:biosynthesis* / Q000235:genetics; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism
C568267:ASIC1 protein, mouse; D062565:Acid Sensing Ion Channels; D009419:Nerve Tissue Proteins; D015222:Sodium Channels