Overview
Hydroxylation: P2, P11, P29
D-amino acid: F - D-Phenylalanine 44
Alomone Labs Iota-conotoxin RXIA affects the activation of NaV1.6 channels expressed in Xenopus oocytes.A. Representative traces of NaV1.6 channel currents before (black) and after the application of 1 µM (magenta) and 10 µM (green) Iota-conotoxin RXIA (#STI-300). Iota-conotoxin RXIA caused a significant current at a voltage that does not normally activates the channel. Membrane potential was held at -100 mV, and a voltage step to -20 mV was applied every 10 sec. B. Representative time course of current amplitude at -20 mV before, during application of 1 µM and 10 µM Iota-conotoxin RXIA (as indicated by bars) and upon wash, demonstrating the current amplitude enhancement.
Iota-conotoxin RXIA (ɩ-Conotoxin RXIA), a peptide toxin originally isolated from Conus radiatus, is a voltage-gated sodium channel activator. The peptide toxin belongs to of the I1-superfamily, which contains eight cysteine residues arranged in a -C-C-CC-CC-C-C- pattern. Iota-RXIA is one of three characterized I1 peptides in which the third to last residue is posttranslationally isomerized to the d configuration. Naturally occurring Iota-conotoxin RXIA with d-Phe44 is significantly more active as an excitotoxin than the l-Phe analogue both in vitro and in vivo although crystallography data has shown the overall structure is only slightly altered by this shift1.
Iota-conotoxin RXIA affects NaV1.6, Nav1.2 and Nav1.7 sodium channels by shifting their voltage dependence of activation to more hyperpolarized potentials2.
NaV channel agonists have been isolated from the venom of different organisms and are also produced by plants, bacteria and algae. These compounds provide key insights into the molecular structure, function and pathophysiological roles of NaV channels and are important tools due to their specific subtype-selectivity1.
