Characterization of the excitatory mechanism induced by Jingzhaotoxin-I inhibiting sodium channel inactivation.
We have recently isolated a peptide neurotoxin, Jingzhaotoxin-I (JZTX-I), from Chinese tarantula Chilobrachys jingzhao venom that preferentially inhibits cardiac sodium channel inactivation and may define a new subclass of spider sodium channel toxins. In this study, we found that in contrast to other spider sodium channel toxins acting presynaptically rather than postsynaptically, JZTX-I augmented frog end-plate potential amplitudes and caused an increase in both nerve mediated and unmediated muscle twitches. Although JZTX-I does not negatively shift sodium channel activation threshold, an evident increase in muscle fasciculation was detected. In adult rat dorsal root ganglion neurons JZTX-I (1 microM) induced a significant sustained tetrodotoxin-sensitive (TTX-S) current that did not decay completely during 500 ms and was inhibited by 0.1 microM TTX or depolarization due to voltage-dependent acceleration of toxin dissociation. Moreover, JZTX-I decreased closed-state inactivation and increased the rate of recovery of sodium channels, which led to an augmentation in TTX-S ramp currents and decreasing the amount of inactivation in a use-dependant manner. Together, these data suggest that JZTX-I acted both presynaptically and postsynaptically and facilitated the neurotransmitter release by biasing the activities of sodium channels towards open state. These actions are similar to those of scorpion alpha-toxin Lqh II.
Xiao
Yucheng
Y
Life Sciences College, Hunan Normal University, Changsha, Hunan 410081, PR China.
Li
Jiang
J
Deng
Meichun
M
Dai
Changliang
C
Liang
Songping
S
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D005260:Female; D005727:Ganglia, Spinal / Q000187:drug effects / Q000502:physiology; D015640:Ion Channel Gating / Q000187:drug effects; D008297:Male; D051379:Mice; D009045:Motor Endplate / Q000502:physiology; D009469:Neuromuscular Junction / Q000187:drug effects; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D026941:Sodium Channel Blockers / Q000494:pharmacology*; D013111:Spider Venoms / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects; D013779:Tetrodotoxin / Q000494:pharmacology
D010455:Peptides; D026941:Sodium Channel Blockers; D013111:Spider Venoms; C500354:jingzhaotoxin-I, Chilobrachys jingzhao; D013779:Tetrodotoxin