Acid-sensing ion channels (ASICs) form a family of voltage-independent amiloride-sensitive cation channels that predominantly conduct Na+ ions. ASICs are activated by extracellular acidification within the physiological range, and they form effective proton sensors in both the central and peripheral nervous system, with increasing evidence of expression in non-neuronal cells as well. Positive modulators include some metal ions, small molecules, neuropeptides, opioid peptides, and a snake toxin, while inhibitors include nonspecific and/or nonsubtype-specific small molecules and more specific natural peptides isolated from animal venoms. A combination of genetic and pharmacologic approaches using the weakly selective inhibitor amiloride and more selective peptide toxins has revealed the implication of ASIC channels in an increasing number of physiological and pathophysiological processes, most of them associated with extracellular pH fluctuations, ranging from synaptic plasticity, learning, memory, fear, depression, seizure termination, and neuronal degeneration to nociception and mechanosensation.WIREs Membr Transp Signal 2013, 2:155–171. doi: 10.1002/wmts.88
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