Acid-sensing ion channel 1b (ASIC1b)

Acid-sensing ion channel 1b (ASIC1b) is a proton-gated, voltage-independent sodium channel belonging to the degenerin/epithelial sodium channel (DEG/ENaC) superfamily [1, 7]. It is a splice variant of the ASIC1 gene (formerly ACCN2) and is primarily expressed in the peripheral nervous system, specifically within the sensory neurons of the dorsal root ganglia [6, 10]. Unlike the ASIC1a variant, which is prominent in the central nervous system, ASIC1b is largely restricted to the periphery, where it serves as a specialized sensor for extracellular acidosis resulting from tissue injury, inflammation, or ischemia [5, 9]. Activation of ASIC1b by a decrease in pH elicits transient sodium currents that depolarize neurons and facilitate the transmission of pain signals [2, 8]. ASIC1b is critically involved in the development and maintenance of various pain conditions, including inflammatory, neuropathic, and chronic muscle pain such as fibromyalgia [5, 6, 8]. Due to its peripheral distribution, it is considered a high-value therapeutic target for analgesia, offering the potential for pain relief with fewer central nervous system side effects than non-selective ASIC inhibitors [10, 15]. Research has identified mambalgins—peptides found in mamba snake venom—as potent inhibitors of ASIC1b-containing channels, demonstrating significant analgesic efficacy in preclinical models [3, 13]. Other known modulators include the non-selective blocker amiloride and the activating toxin MitTX, which induces pain by triggering the channel [10, 11].

Other names

ASIC1.2ASIC-betaASIC-βACCN2Amiloride-sensitive cation channel 2 (splice variant b)BNaC2

Inhibition of proton-gated sodium currents through pore blockade or stabilization of the desensitized state