Jingzhaotoxin proteins are part of a venom secreted by Chilobrachys jingzhao, the Chinese tarantula. and act as neurotoxins. There are several subtypes of jingzhaotoxin, which differ in terms of channel selectivity and modification characteristics. All subspecies act as gating modifiers of sodium channels and/or, to a lesser extent, potassium channels. Sources Chilobrachys jingzhao, also known as the Chinese earth tiger tarantula or Chilobrachys guangxiensis, can be found in China and Asia. This large tarantula belongs to the family of Theraphosidae. Chemistry Jingzhaotoxins reported on this page are 29-36-residue polypeptides with varying numbers of stabilizing disulfide bridges. Target Jingzhaotoxins can target multiple channels. The following IC50 values have been determined: '*' Only a dissociation constant (Kd) was measured. Kd; 0.43 μM '**' Only a Kd was measured. Kd; 1.28 μM '***' Only a Kd was measured. Kd; 0.74 μM Mode of action JZTX-I Effect on voltage-gated sodium channels (VGSC) JZTX-I preferentially acts on cardiac sodium channels, but also affects tetrodotoxin-sensitive (TTX-S) voltage-gated sodium channels (VGSC) in dorsal root ganglion (DRG) neurons. It modifies the sodium current by inhibiting channel inactivation and speeding up recovery after inactivation. JZTX-I does not affect the activation threshold of sodium channels. Effect on potassium channels JZTX-I has a modest effect on potassium currents by slowing the rate of activation of Kv2.1 and Kv4.1 channels and increasing the tail current deactivation. JZTX-II Effect on VGSC JZTX-II has high affinity to the tetrodotoxin-resistant (TTX-R) VGSC in cardiac myocytes where it significantly slows rapid inactivation. Although JZTX-II does not have an effect on TTX-R neuronal channels in DRG neurons it does affect TTX-S sodium currents by slowing down their inactivation. Effect on potassium channels At this point, the effects of JZTX-II on potassium channels are unknown. JZTX-III Effect on VGSC JZTX-III has a high affinity to the TTX-R Nav1.5 voltage gated sodium channel which is expressed in cardiac myocytes but not in neurons. It modifies the sodium channel current by shifting its activation curve to a more depolarized voltage without affecting its inactivation curve. JZTX-II is docked to the Nav1.5 DIIS3-4 linker, which is responsible for its high selectivity. Effect on potassium channels JZTX-III modifies the voltage gated Kv2.1 potassium channel in cardiac myocytes and can bind to both open and closed channels. It modifies the gating of Kv2.1 channel by shifting the activation curve to a more depolarized voltage and by speeding up deactivation. JZTX-IV Effect on VGSC