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Acid-Sensing Ion Channels Family

Acid-sensing ion channels (ASICs) are a subfamily of epithelial sodium channel (ENaC)-degenerin superfamily of ion channels. Each member of the ASICs family consists of a 500-560 amino acid sequence. The sequence forms a six-pass membrane region, a large extracellular domain, and a cytoplasmic amino-carboxyl terminus that is very important for the channel's intracellular protein interactions and modulations, ion permeability, and gating. ASIC proteins are most detected in the nervous system involved in the regulation of neural plasticity. They function as a sensor of reduced levels of extracellular pH and response to the signal from the neuron. Activated ASIC proteins by extracellular protons can induce their conformational change thereby promoting the influx of sodium ions. Besides, the only variant ASIC1a shows low Ca2+ permeability. Most studies have shown that ASIC proteins play a key role in the progression of many diseases, such as ischemia, multiple sclerosis, and seizures.

There are 5 subtypes (ASIC1-5) in the ASICs family, encoded by ASIC1, ASIC2, ASIC3, ASIC4 and ASIC5 gene respectively. As proton-gated cation channels in the brain, they exert trafficking and synaptic function, involved in the regulation of multiple physical processes, such as pain, taste, and gastrointestinal functions. Most studies have revealed that targeting ASICs family may provide a new therapeutic strategy for neurological diseases. However, the study of ASICs physical functions is still lacking and ASIC4 has no known function yet. The following table shows four members of ASICs family.

Human ASICs Family Members
ASIC1 ASIC2 ASIC3 ASIC4

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