Psalmotoxin 1 (PcTx1) is a protein toxin that can bind at subunit-subunit interfaces of acid-sensing ion channel 1a (ASIC1a). Psalmotoxin 1 is a potent and selective ASIC1a inhibitor (IC₅₀: 0.9 nM) by increasing the apparent affinity for H⁺ of ASIC1a. Psalmotoxin 1 can induce cell apoptosis, also inhibits cell migration, proliferation and invasion of cancer cells. Psalmotoxin 1 can be used in the research of cancers, or neurological disease.
This toxin is a gating modifier that acts principally as an inhibitor on ASIC1a (ASIC isoform 2) and a potentiator on ASIC1b (ASIC isoform 3). This toxin potently and selectively inhibits rat, mouse and human ASIC1a (IC50=0.35-3.7 nM). The blockade is rapidly reversible. The toxin acts by shifting its steady-state desensitization to more alkaline pH (0.27 pH unit). At higher concentrations, it potentiates rat and human ASIC1b and activates chicken ASIC1 by stabilizing the open state of these subtypes. The toxin binds most tightly to the open and the desensitized states of ASIC1a (promoting desensitization), whereas it binds most tightly to the open state of ASIC1b (promoting opening). The toxin also inhibits mouse ASIC1a-ASIC2b (IC50=2.64 nM) and rat ASIC1a-ASIC2a. It binds to the extracellular domain at subunit interfaces in the acidic pocket with the majority of contacts on the thumb domain of the channel. It is also noteworthy that calcium competes with the toxin, probably by inhibiting binding of the toxin to the channel.