High-density expression of Ca2+-permeable ASIC1a channels in NG2 glia of rat hippocampus

• Published in: PloS one 2010-09, Vol.5 (9), p.e12665
• Main Authors: Lin, Yen-Chu, Liu, Yu-Chao, Huang, Yu-Yin, Lien, Cheng-Chang
• Format: Article
• Language: English
• Subjects: Acid Sensing Ion Channels; Acidity; Acidosis; Acids; Activation; Amino acids; Animals; Brain; Brain injury; Brain research; Calcium (intracellular); Calcium - metabolism; Calcium channels; Calcium imaging; Calcium influx; Calcium permeability; Cell Biology/Neuronal and Glial Cell Biology; Cells, Cultured; Central nervous system; Chemical sensors; Chemoreceptors; Density; Depolarization; Electrophysiology; Experiments; Gene Expression; Glial cells; Hippocampus; Hippocampus - chemistry; Hippocampus - metabolism; Hydrogen ions; Immunocytochemistry; Ion channels; Ischemia; Laboratory animals; Localization; Membrane potential; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Nervous system; Neuroglia - chemistry; Neuroglia - metabolism; Neuroimaging; Neurological diseases; Neurons; Neuroscience; Neurosciences; Permeability; pH effects; Physiology/Neuronal Signaling Mechanisms; Proteins; Rats; Rats, Sprague-Dawley; Rodents; Seizures; Sodium channels; Sodium Channels - genetics; Sodium Channels - metabolism; Subunit structure; Trends
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0012665

NG2 cells, a fourth type of glial cell in the mammalian CNS, undergo reactive changes in response to a wide variety of brain insults. Recent studies have demonstrated that neuronally expressed acid-sensing ion channels (ASICs) are implicated in various neurological disorders including brain ischemia and seizures. Acidosis is a common feature of acute neurological conditions. It is postulated that a drop in pH may be the link between the pathological process and activation of NG2 cells. Such postulate immediately prompts the following questions: Do NG2 cells express ASICs? If so, what are their functional properties and subunit composition? Here, using a combination of electrophysiology, Ca2+ imaging and immunocytochemistry, we present evidence to demonstrate that NG2 cells of the rat hippocampus express high density of Ca2+-permeable ASIC1a channels compared with several types of hippocampal neurons. First, nucleated patch recordings from NG2 cells revealed high density of proton-activated currents. The magnitude of proton-activated current was pH dependent, with a pH for half-maximal activation of 6.3. Second, the current-voltage relationship showed a reversal close to the equilibrium potential for Na+. Third, psalmotoxin 1, a blocker specific for the ASIC1a channel, largely inhibited proton-activated currents. Fourth, Ca2+ imaging showed that activation of proton-activated channels led to an increase of [Ca2+]i. Finally, immunocytochemistry showed co-localization of ASIC1a and NG2 proteins in the hippocampus. Thus the acid chemosensor, the ASIC1a channel, may serve for inducing membrane depolarization and Ca2+ influx, thereby playing a crucial role in the NG2 cell response to injury following ischemia.