Acid-sensing ion channel 1 (ASIC1)

Acid-sensing ion channel 1 (ASIC1) is a neuronally expressed, proton-gated cation channel belonging to the epithelial sodium channel/degenerin (ENaC/DEG) superfamily[1][3]. It forms trimers that open in response to drops in extracellular pH by directly sensing protons via a specialized extracellular domain called the acidic pocket[4]. ASIC1 is highly permeable to sodium ions, with the ASIC1a isoform also allowing low-level calcium entry[1][2]. Rapid activation of ASIC1 (particularly ASIC1a) leads to transient neuronal excitation and is critically involved in diverse physiological processes such as synaptic plasticity, pain sensation, and learning and memory[3]. Pathologically, excessive activation of ASIC1 during tissue acidosis mediates cell death and contributes to ischemic brain injury, neurodegeneration, pain, and possibly psychiatric conditions[1][3]. Several small-molecule inhibitors and venom-derived peptide toxins (such as PcTx1) modulate ASIC1 activity and form the basis for potential drug development targeting neurological and pain disorders[4][5]. However, due to its fundamental role in central nervous system signaling, therapeutic targeting requires cell and context specificity to avoid undesired neurophysiological effects[3].

Other names

Acid-sensing ion channel 1a proteinAmiloride-sensitive cation channel 2, neuronalBrain sodium channel 2ACCN2ASICBNaC2BNAC2hBNaC2

Inhibition of ion conductance (blockade of sodium and/or calcium entry through the channel) Allosteric modulation resulting in conformational stabilization of the closed/desensitized state Competitive antagonism at proton-binding or toxin-binding sites