Overview
- Bosmans, F. et al. (2006) Mol. Pharmacol. 69, 419.
Alomone Labs Ceratotoxin-1 blocks NaV1.2 currents heterologously expressed in Xenopus oocytes.A. Time course of Ceratotoxin-1 (#STC-680) action on maximum current NaV1.2 amplitude. Maximum peak current amplitudes were plotted as a function of time. Membrane potential was held at -100 mV and oocytes were stimulated by a 100 ms voltage step to -10 mV. 200 nM Ceratotoxin-1 was perfused as indicated by the bar (green) for 200 sec. B. Superimposed examples of NaV1.2 channel peak current in the absence (control) and presence (green) of 200 nM Ceratotoxin-1(taken from the experiment in A).
There are currently nine types of voltage-gated Na+ (NaV) channels defined and characterized. The channels are responsible for propagation and the creation of action potential in excitable cells1. The channel is comprised of the main α subunit and the β auxiliary subunits. Although the α subunit is sufficient for channel expression it is the β subunit that modifies the kinetics and voltage dependency of the channel. The α subunits are organized in four homologous domains (I-IV) each containing six transmembrane α helices (S1-S6)2.
Ceratotoxin-1 (β-theraphotoxin-Cm1a, β-TRTX-Cm1a, CcoTx1) is a NaV channel blocker. This peptide toxin was originally isolated from the spider species Ceratogyrus marshalli (Straighthorned baboon tarantula). The toxin binds to all NaV channels in the central nervous system apart from NaV1.33. Mice injected with 500 pmol of Ceratotoxin-1 exhibited symptoms of neurological toxicity in the form of difficulty of standing, breathing reduction and flaccid paralysis. Ceratotoxin-1 also decreases Na+ influx in NaV1.1, NaV1.2, NaV1.4. It is especially selective for NaV1.2 with an IC50 value of 3±1 nM3.
