Jingzhaotoxin-IX

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 Na_V channels, tetrodotoxin-resistant and tetrodotoxin-sensitive isoforms and K_V2.1 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 (K_v2.1) and the voltage-gated sodium channel (Na_V). 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.