Overview
Trp33 – amidation
- Sanguinetti, M.C. et al. (1997) Mol. Pharmacol. 51, 491.
- Zhou X. et al. (2020) Nature Comm. Vol. 11, 2293.
Alomone Labs Heteropodatoxin-1 inhibits NaV1.7 channel currents heterologously expressed in Xenopus oocytes.A. Representative time course of Heteropodatoxin-1 (#STH-320) inhibition of NaV1.7 channels current. Membrane potential was held at -100 mV, current was elicited by a 100 ms voltage step to -10 mV every 10 sec, and significantly inhibited by application of 4 µM
Heteropodatoxin-1 (green).B. Superimposed traces of NaV1.7 channel current in the absence (control) and presence (green) of 4 µM Heteropodatoxin-1 (taken from the recording in A).
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 Nav1.7, Nav1.8 and Nav1.9, 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.
