Acid-sensing ion channels in acidosis-induced injury of human brain neurons.
Acidosis is a common feature of the human brain during ischemic stroke and is known to cause neuronal injury. However, the mechanism underlying acidosis-mediated injury of the human brain remains elusive. We show that a decrease in the extracellular pH evoked inward currents characteristic of acid-sensing ion channels (ASICs) and increased intracellular Ca(2+) in cultured human cortical neurons. Acid-sensing ion channels in human cortical neurons show electrophysiological and pharmacological properties distinct from those in neurons of the rodent brain. Reverse transcriptase-PCR and western blot detected a high level of the ASIC1a subunit with little or no expression of other ASIC subunits. Treatment of human cortical neurons with acidic solution induced substantial cell injury, which was attenuated by the ASIC1a blockade. Thus, functional homomeric ASIC1a channels are predominantly expressed in neurons from the human brain. Activation of these channels has an important role in acidosis-mediated injury of human brain neurons.
Li
Minghua
M
Robert S. Dow Neurobiology Laboratories, Legacy Research, Portland, Oregon 97232, USA.
Inoue
Koichi
K
Branigan
Deborah
D
Kratzer
Eric
E
Hansen
Jillian C
JC
Chen
Jeff W
JW
Simon
Roger P
RP
Xiong
Zhi-Gang
ZG
D062565:Acid Sensing Ion Channels; D000138:Acidosis / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D009474:Neurons / Q000378:metabolism*; D012377:Rodentia / Q000378:metabolism; D015222:Sodium Channels / Q000096:biosynthesis*; D013045:Species Specificity
C568266:ASIC1 protein, human; D062565:Acid Sensing Ion Channels; D009419:Nerve Tissue Proteins; D015222:Sodium Channels