Overview
- Deng, M. et al. (2009) Neuropharmacology 57, 77.
Alomone Labs Jingzhaotoxin-IX blocks NaV1.5 channels heterologously expressed in Xenopus oocytes.A. Time course of Jingzhaotoxin-IX (#STJ-300) action on NaV1.5 currents. Peak current amplitude at -20 mV was plotted as a function of time. Membrane potential was held at -100 mV and oocytes were stimulated by a 50 ms voltage step to -20 mV. 1 µM Jingzhaotoxin-IX (applied for 4.5 min, green) was perfused during the period marked by the bar. B. Superimposed traces of channel current in the absence (black) and presence (green) of 1 µM Jingzhaotoxin-IX (taken from experiment in A).
Jingzhaotoxin-IX (JZTX-IX) is a neurotoxin, C-terminally amidated peptide composed of 35 amino acid residues. JZTX-IX was originally purified from the venom of the tarantula Chilobrachys jingzhao, one of the most venomous spiders in China.
Jingzhaotoxin-IX interacts with several types of ion channels, such as NaV channels, tetrodotoxin-resistant and tetrodotoxin-sensitive isoforms and KV2.1 channels.
Binding of JZTX-IX toxin to the ion channel can shift the voltage dependence of channel activation to a more positive voltage and is not reversible by extreme depolarization. 10 μM of the toxin is sufficient for a total blockade of the ion channels at resting point without pulsing.
JZTX-IX has confirmed activity at ion channels known to be important for pancreatic beta-cell function and insulin signaling, such as the delayed potassium rectifier channel (Kv2.1) and the voltage-gated sodium channel (NaV). The peptide is believed to adopt a characteristic inhibitor cysteine knot (ICK) structure as a result of the six cysteine residues present, which is considered to provide effective resistance against circulating enzymatic breakdown and increase therapeutic utility. JZTX-IX has been shown to significantly increase intracellular calcium influx in beta-cells without directly inducing beta-cell depolarization, as well as increase beta-cell proliferation and protect against cytokine-induced beta-cell apoptosis. Jingzhaotoxin IX has also been shown to augment exenatide-induced appetite suppressive actions and enhance the ability of exenatide to curb appetite in overnight fasted mice2.
