科研之友
微信
新浪微博
Facebook
分享链接
摘要
In the last decades, Ts1 has not only been the subject of many studies, it has also been considered as a very useful tool to investigate Na-V channels and to explore the exact role of Na-V channels in channelopathies. Ts1 is believed to modulate the activation process of Na-V upon interaction at the neurotoxin binding site 4. Our aim was to carry out an in depth functional characterization of Ts1 on a wide array of Na-v channels, in order to investigate its mechanism of action and to verify if Ts1 can indeed be considered as a prototype site 4 selective toxin, valid for all the Na-v isoforms we know currently. Ts1 has been subjected to an in-depth functional investigation on 9 Na-V isoforms expressed in Xenopus laevis oocytes. Ts1 does not only interfere with the activation process but also modulates the inactivation in a bell-shaped voltage-dependent matter. Furthermore, Ts1 altered the ion selectivity through insect Na-V. without influencing the tetrodotoxin selectivity of the channels. Finally, Ts1 was also found to inhibit the sodium current through the cardiac Na(v)1.5 isoform. On the basis of the totally unexpected plethora of Na-v modulations as induced by Ts1, we demonstrate that caution is required in interpretation the in vivo experiments when using Ts1. The electrophysiological characterization of Ts1 indeed shows that the general accepted contours of Na-V binding sites are much more obscure than believed and that interpretation of Na-V pharmacology upon toxin binding is more complex than believed thus far.
- 出版日期2015-8
