Heteropodatoxin-1 (HpTX1 or kappa-sparatoxin-Hv1a) is a peptide toxin originally isolated from Heteropoda venatoria, a spider species that is mostly present in tropical regions of the world. This toxin belongs to the Heteropoda toxins family that includes HpTX1, HpTX2 and HpTX3, all of which were shown to be Kv4.2 voltage gated potassium channel inhibitors¹.

Recently it has been found that HpTX1 is a Nav channel pharmacological tool as well. HpTX1 inhibits Nav1.7 and activates Nav1.9, but has no effect on Nav1.8 channel².

The voltage-gated sodium channels Na_v1.7, Na_v1.8 and Na_v1.9, preferentially expressed in the peripheral terminals of sensory neurons and are critical for pain perception in peripheral nociceptors³. Loss of function of Nav1.7 leads to congenital insensitivity to pain in humans². Genetic and functional studies have illustrated that mutations in Nav1.8 and Nav1.9 cause human pain disorders, providing direct clinical evidence linking these two channels to human pain. Considering that the three channels play distinct roles in the generation and propagation of action potentials, they might regulate pain signaling cooperatively. HpTx1-induced hypersensitivity is mediated by Nav1.9 activation and offers pharmacological insight into the relationship of the three Nav channels in pain signaling².