Acid-sensitive ion channels

1. Acid-sensitive ion channels Acid-sensitive ion channels (ASICs) are a class of cation channels activated by extracellular acidification. Currently, six ASICs have been discovered, which are widely expressed in the peripheral and central nervous systems. Techniques such as gene knockout, have proven that they play an important role in tactile, pain, sour taste, learning and memory. At the same time, they are also involved in certain pathological reactions. ASICs can be regulated by neuropeptides, temperature, metal ions and ischemic related substances, thereby integrating the cells around them. There have been a variety of signals to regulate its function. ASICs are a branch of the NaC (Na+ channel)/DEG (degenerin) superfamily. Like other members of the family, ASICs may consist of four subunits, each consisting of more than 500 amino acids, whose structure contains two hydrophobic transmembrane regions, a large cysteine-rich extracellular loop and intracellular N-terminus and C-terminus. Four conserved regions in this structure play an important role in the function of ASICs. The second transmembrane segment (TM2) forms a pore lining; nine conserved amino acid sequences near the medial segment of TM1 affect channel openness probability, ion permeability, and Na+ selectivity. The extracellular proximity to TM2 (Gly430) mutation leads to the continuous opening of the channel, indicating that this region is related to the gating of the channel; a cysteine-rich conserved fragment in the extracellular domain is involved in maintaining the basic function of the channel. ASICs are widely distributed in vivo, but different subunits are distributed in specificity.