PubMed 25784299

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Nav1 , Nav1.3

Title: Synergetic action of domain II and IV underlies persistent current generation in Nav1.3 as revealed by a tarantula toxin.

Authors: Cheng Tang, Xi Zhou, Yunxiao Zhang, Zhaohua Xiao, Zhaotun Hu, Changxin Zhang, Ying Huang, Bo Chen, Zhonghua Liu, Songping Liang

Journal, date & volume: Sci Rep, 2015 , 5, 9241

PubMed link:

The persistent current (INaP) through voltage-gated sodium channels enhances neuronal excitability by causing prolonged depolarization of membranes. Nav1.3 intrinsically generates a small INaP, although the mechanism underlying its generation remains unclear. In this study, the involvement of the four domains of Nav1.3 in INaP generation was investigated using the tarantula toxin α-hexatoxin-MrVII (RTX-VII). RTX-VII activated Nav1.3 and induced a large INaP. A pre-activated state binding model was proposed to explain the kinetics of toxin-channel interaction. Of the four domains of Nav1.3, both domain II and IV might play important roles in the toxin-induced INaP. Domain IV constructed the binding site for RTX-VII, while domain II might not participate in interacting with RTX-VII but could determine the efficacy of RTX-VII. Our results based on the use of RTX-VII as a probe suggest that domain II and IV cooperatively contribute to the generation of INaP in Nav1.3.