PMID- 17618665 OWN - NLM STAT- MEDLINE DCOM- 20071109 LR - 20070911 IS - 0041-0101 (Print) IS - 0041-0101 (Linking) VI - 50 IP - 4 DP - 2007 Sep 15 TI - Characterization of the excitatory mechanism induced by Jingzhaotoxin-I inhibiting sodium channel inactivation. PG - 507-17 AB - 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. FAU - Xiao, Yucheng AU - Xiao Y AD - Life Sciences College, Hunan Normal University, Changsha, Hunan 410081, PR China. FAU - Li, Jiang AU - Li J FAU - Deng, Meichun AU - Deng M FAU - Dai, Changliang AU - Dai C FAU - Liang, Songping AU - Liang S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20070503 PL - England TA - Toxicon JT - Toxicon : official journal of the International Society on Toxinology JID - 1307333 RN - 0 (Peptides) RN - 0 (Sodium Channel Blockers) RN - 0 (Spider Venoms) RN - 0 (jingzhaotoxin-I, Chilobrachys jingzhao) RN - 4368-28-9 (Tetrodotoxin) SB - IM MH - Action Potentials/drug effects MH - Animals MH - Female MH - Ganglia, Spinal/drug effects/physiology MH - Ion Channel Gating/drug effects MH - Male MH - Mice MH - Motor Endplate/physiology MH - Neuromuscular Junction/drug effects MH - Peptides/*pharmacology MH - Rats MH - Rats, Sprague-Dawley MH - Sodium Channel Blockers/*pharmacology MH - Spider Venoms/*pharmacology MH - Synaptic Transmission/drug effects MH - Tetrodotoxin/pharmacology EDAT- 2007/07/10 09:00 MHDA- 2007/11/10 09:00 CRDT- 2007/07/10 09:00 PHST- 2007/02/11 00:00 [received] PHST- 2007/04/15 00:00 [revised] PHST- 2007/04/23 00:00 [accepted] PHST- 2007/07/10 09:00 [pubmed] PHST- 2007/11/10 09:00 [medline] PHST- 2007/07/10 09:00 [entrez] AID - S0041-0101(07)00163-8 [pii] AID - 10.1016/j.toxicon.2007.04.018 [doi] PST - ppublish SO - Toxicon. 2007 Sep 15;50(4):507-17. doi: 10.1016/j.toxicon.2007.04.018. Epub 2007 May 3.