Overview
Ser66 - amidation
- Schiavon, E. et al. (2006) J. Biol. Chem. 281, 20326.
Centrifuge all products before use (10000 x g 5 min).
Alomone Labs Cn2 Toxin activates Nav1.6 channels expressed in Xenopus oocytes.A. Representative traces of Nav1.6 channel currents before and after application of 100 nM (magenta) and 500 nM (green) Cn2 Toxin (#STC-060). Cn2 Toxin caused a significant current at a voltage that does not normally activate the channels. A double protocol with an initial holding potential of -120 mV was conditioned by a prepulse of +35 mV for 20 ms, while the second pulse to -40 mV for 50 ms was preceded by 30 ms at -100 mV.
B. Representative time course of current amplitude at -40 mV before, during application of 100 nM and 500 nM Cn2 Toxin (indicated by bars) and upon wash, demonstrating the current amplitude enhancement.
Cn2 Toxin is a β-scorpion toxin, isolated from the venom of Centruroides noxius, a Mexican native scorpion species. It belongs to the scorpion β-toxins family that bind to the voltage-sensing domain of voltage-gated sodium (NaV) channels and trap the voltage-sensing domain in the activated state1. This unique toxin is capable of simultaneously inducing both the left shift voltage-dependent activation and a transient resurgent current only in human NaV1.6 channels, among the other TTX-sensitive isoforms2. Cn2 also produced both actions in mouse cerebellar Purkinje neurons and blocked firing at appropriate concentrations2.
NaV1.6 plays an essential role in peripheral sensory neurons, specifically at the distal terminals of mechanosensing fibers innervating the skin and colon. NaV1.6 activation by Cn2 Toxin leads to enhanced response to mechanical stimulus in vivo3. Cn2 Toxin facilitates Nav1.6 early channel opening, and increased persistent and resurgent currents in large-diameter DRG neurons in a unique mechanism of action3.
Cn2 Toxin was described also as a modifier of the neuronal structure and induces apoptosis and reduction of the proliferation and cell survival in experiments performed in F11 mouse neuroblastoma cells4.
The crystal structure of this toxin was determined and it was shown to be a 66 amino acid polypeptide that shares a similar structure with other scorpion toxins acting on sodium channels. It is made of a triple-stranded antiparallel β-sheet and an α-helix, and is stabilized by four disulfide bridges. It contains a hydrophobic core, a hydrophobic patch and a positively charged patch5,6.
