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) (PubMed:10829030, PubMed:15955877, PubMed:21036899). This toxin potently and selectively inhibits rat, mouse and human ASIC1a (IC(50)=0.35-3.7 nM) (PubMed:10829030, PubMed:15955877, PubMed:21715637, PubMed:26248594, PubMed:21825095). The blockade is rapidly reversible (PubMed:10829030, PubMed:28320941). The toxin acts by shifting its steady-state desensitization to more alkaline pH (0.27 pH unit) (PubMed:15955877, PubMed:16505147). At higher concentrations, it potentiates rat and human ASIC1b and activates chicken ASIC1 by stabilizing the open state of these subtypes (PubMed:16505147, PubMed:21036899, PubMed:19185346, PubMed:24262969, PubMed:22842900). 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) (PubMed:16505147). The toxin also inhibits mouse ASIC1a-ASIC2b (IC(50)=2.64 nM) and rat ASIC1a-ASIC2a (PubMed:21715637, PubMed:27277303). 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 (PubMed:21825095, PubMed:22842900, PubMed:22760635). It is also noteworthy that calcium competes with the toxin, probably by inhibiting binding of the toxin to the channel (PubMed:15955877). Expressed by the venom gland. The presence of a 'disulfide through disulfide knot' structurally defines this protein as a knottin. This toxin has been shown to be neuroprotective in both rodent and porcine models of cerebral ischemia when administered 30 minutes prior to induction of stroke (PubMed:28457973). In addition, a single dose of this toxin (1 ng/kg, i.c.v. 2 hours post stroke) does indeed provide substantial neuronal and functional protection in ischemic stroke in conscious hypertensive rats (PubMed:26320544). This peptide is present at only 0.4% abundance in P.cambridgei venom. Does not act on rat and mouse ASIC1a-ASIC2a (PubMed:10829030, PubMed:21715637). Does not act on rat ASIC1a-ASIC3 (PubMed:10829030). Belongs to the psalmotoxin-1 family.