Acid-sensing ion channels in acidosis-induced injury of human brain neurons.
Acid-sensing ion channels in acidosis-induced injury of human brain neurons.
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DOI：
10.1038/jcbfm.2010.30
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发表时间：
2010-06
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Acidosis is a common feature of human brain during ischemic stroke and is known to independently cause neuronal injury. However, the mechanism underlying acidosis-mediated injury of human brain remains elusive. We show that lowering the extracellular pH evoked inward currents characteristic of acid-sensing ion channels (ASICs) and increased intracellular Ca2+ in cultured human cortical neurons. ASICs in human cortical neurons show electrophysiological and pharmacological properties distinct from neurons in rodent brain. RT-PCR and Western blot detected high level of 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 ASIC1a blockade. Thus, functional homomeric ASIC1a channels are predominantly expressed in neurons from human brain. Activation of these channels plays an important role in acidosis-mediated injury of human brain neurons.
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