title: The effect of recombinant neurotoxins from the sea anemone Anthopleura sp. on sodium currents of rat cerebral cortical neurons.
abstract: We have investigated the action of the recombinant neurotoxins, named Hk7a and Hk2a, whose amino acid sequences differ only in two positions, isolated from the sea anemone Anthopleura sp., on neuronal sodium currents using the whole-cell voltage-clamp techniques. The rat cerebral cortical neurons in primary culture were used for this study. In our experiments, these cells all express tetrodotoxin-sensitive (TTX-S) sodium currents. Under the voltage-clamp condition, application of Hk7a and Hk2a reduced the sodium channel current amplitude and shifted the voltage dependence of activation to more positive potential; while Hk7a produced no significant effect on the voltage at which 50% of the channels were inactivated, Hk2a caused profound hyperpolarizing shift of the voltage-dependent inactivation. Also, both Hk7a and Hk2a increased the time course of recovery from inactivation. In kinetic studies, whereas application of Hk2a slows the time to peak of voltage-gated sodium channel, the time course of fast and slow inactivating component, no significant effect was observed in Hk7a. These results suggested that the difference of key amino acid between Hk7a and Hk2a might contribute to their different action; therefore, they could be used as pharmacological tool to study the structure and function of voltage-gated sodium channel.
authors.affiliation: School of Life Sciences, Sun Yat-sen (Zhongshan) University, Guangzhou, Guangdong Province 510275, People's Republic of China. lssxh@mail.sysu.edu.cn
authors.forename: Hui
authors.initials: H
authors.lastname: Xiang
authors.forename: Wucheng
authors.initials: W
authors.lastname: Tao
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.forename: Anlong
authors.initials: A
authors.lastname: Xu
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000166:cytology*; D003064:Cnidarian Venoms / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects; D007700:Kinetics; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D009498:Neurotoxins / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology*; D012615:Sea Anemones / Q000737:chemistry*; D015222:Sodium Channels / Q000378:metabolism*; D013997:Time Factors
chemical_list: D003064:Cnidarian Venoms; D009498:Neurotoxins; D011994:Recombinant Proteins; D015222:Sodium Channels