Overview
- Tao, H. et al. (2016) Toxicon 124, 8.
Alomone Labs Jingzhaotoxin XI blocks KV2.1 channels expressed in Xenopus oocytes.A. Representative time course of Jingzhaotoxin XI (#STJ-400) inhibition of KV2.1 current. Membrane potential was held at -80 mV, current was elicited by a 300 ms voltage step to +10 mV every 10 sec, and inhibited by 0.1 µM and 1 µM Jingzhaotoxin XI, applied as indicated by horizontal bars. B. Superimposed traces of KV2.1 current after the application of control, 0.1 µM and 1 µM Jingzhaotoxin XI (taken from experiment in A).
Alomone Labs Jingzhaotoxin XI blocks NaV1.5 channels expressed in Xenopus oocytes.A. Representative time course of Jingzhaotoxin XI (#STJ-400) inhibition of NaV1.5 current. Membrane potential was held at -100 mV, current was elicited by a 100 ms voltage ramp to +40 mV every 10 sec, and inhibited significantly by 1 µM Jingzhaotoxin XI. B. Superimposed traces of NaV1.5 current following the application of control and of 1 µM Jingzhaotoxin XI (taken from experiment in A).
Jingzhaotoxin XI (JzTx-XI) is a 34-residue peptide toxin originally isolated from the Chinese tarantula Chilobrachys jingzhao venom. Jingzhaotoxin XI toxin can potently inhibit both voltage-gated Na+ channel NaV1.5 with an IC50 value of 124 ± 26 nM and voltage-gated K+ channel KV2.1 with an IC50 value of 390 ± 60 nM1,2,3.
The mature toxin contains six cysteine residues linked through disulfide bridges and a hydrophobic patch surrounded by charged residues such as Arg or Lys. Jingzhaotoxin XI is a useful tool for investigating the promiscuity of spider toxins2.
JzTx-XI 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-XI has been shown to increase intracellular calcium influx in beta-cells, although less effectively than Jingzhaotoxin IX (#STJ-300), without directly inducing beta-cell depolarization, as well as protect against cytokine-induced beta-cell apoptosis. Jingzhaotoxin XI has also been shown to augment exenatide-induced appetite suppressive actions and enhance the ability of exenatide to curb appetite in overnight fasted mice4.
KV2.1 channels play an important role in neuronal systems including the neural retina. The channel’s functions include regulation of neuronal excitability and neural transmitter release5.
NaV1.5 channels are important in generating and propagating action potentials in excitable cells, in working myocardium and cardiac tissue conduction cells6.
