Heterodimer: MitTx, a heteromeric complex between Kunitz- and phospholipase-A2-like proteins, potently, persistently and selectively activates rat and chicken acid-sensing ion channel ASIC1 (PubMed:22094702, PubMed:24507937). Both alternatively spliced rat isoforms ASIC1a and ASIC1b are activated, with a higher potency for ASIC1a (EC(50)=9.4 nM) vs ASIC1b (EC(50)=23 nM) (PubMed:22094702). The rat ASIC3 subtype is also sensitive to the heterodimer, but with a lower potency (EC(50)=830 nM) (PubMed:22094702). On rat ASIC2a, the toxin shows a very weak activation, but produces a remarkable potentiation (>100-fold) of protons when the extracellular pH drops below neutrality (PubMed:22094702). Moderate and weak activations are also observed on the heterotrimers Asic1a-Asic2a and Asic1a-Asic3 (expressed in CHO cells), respectively (PubMed:22094702). The binding sites of the beta subunit of MitTx and the spider psalmotoxin-1 toxin overlap, explaining why these toxins are mutually exclusive (PubMed:22094702. PubMed:24507937). In vivo, the heterodimer elicits robust pain-related behavior in mice by activation of ASIC1 channels on capsaicin-sensitive nerve fibers (PubMed:22094702). Monomer: does not have phospholipase A2 activity but may maintain some lipid-binding character from its PLA2 lineage, which could aid in effecting neuronal depolarization. Heterodimer of an alpha (Kunitz-type) and a beta (phospholipase A2 homolog) chains; non-covalently-linked. Expressed by the venom gland. The toxin-channel complex has a triskelion-like shape with one toxin heterodimer radiating from each ASIC1 subunit. Toxin subunits protrude from the edges of the channel trimer, with each heterodimer interacting almost exclusively with a single subunit. The heterodimeric toxin does not affect ASIC2b, ASIC4, Kv2.1/KCNB1, Cav3.3/CACNA1I, ENaC alpha/beta/gamma (SCNN1A/SCNN1B/SCNN1G), TRPA1, TRPV1, TRPV3, TRPM8, P2X2/P2RX2, and 5-HT3/HTR3A channels. Belongs to the phospholipase A2 family. Group I subfamily. K49 sub-subfamily. Does not bind calcium as one of the calcium-binding sites is lost (Asp->Lys in position 77, which corresponds to 'Lys-49' in the current nomenclature). The poison in pain - Issue 140 of July 2012