A Nonproton Ligand Sensor in the Acid-Sensing Ion Channel

  title={A Nonproton Ligand Sensor in the Acid-Sensing Ion Channel},
  author={Ye Yu and Zhi Chen and Wei-Guang Li and Hui Cao and En-Guang Feng and Fang Yu and Hong Liu and Hualiang Jiang and Tian-le Xu},
Acid-sensing ion channels (ASICs) have long been considered as extracellular proton (H(+))-gated cation channels, and peripheral ASIC3 channels seem to be a natural sensor of acidic pain. Here, we report the identification of a nonproton sensor on ASIC3. We show first that 2-guanidine-4-methylquinazoline (GMQ) causes persistent ASIC3 channel activation at the normal pH. Using GMQ as a probe and combining mutagenesis and covalent modification analysis, we then uncovered a ligand sensor lined by… CONTINUE READING
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