JZTX-V Targets the Voltage Sensor in Kv4.2 to Inhibit Ito Potassium Channels in Cardiomyocytes

Conclusion In conclusion, JZTX-V effectively inhibited the Ito current and extended theAPD. The molecular mechanism underlying the inhibitory action of JZTX-V on Ito may involve recognition of a conserved binding motif on the S3–S4 linker. Hydrophobic force plays an important role in interactions between the toxin and channel, and the extracellular conformational space of Kv4 modulates toxin affinity. Moreover, the phospholipid membrane may be involved in binding to toxin. These findings broadened our understanding of the effects of JZTX-V on cardiac electrophysiology and further clarified the molecular mechanisms underlying the inhibitory action of JZTX-V on Ito potassium channels, supporting its development as a potential novel antiarrhythmic drug. Ethics Statement SD rats (Hunan SJA Laboratory Animal Co., Ltd., Changsha, China) were used according to the guidelines of the National Institutes of Health for Care and Use of Laboratory Animals. The experiments were approved by the Animal Care and Use Committee of Hunan Normal University. Author Contributions YZ and JL designed the research. YZ and JH performed the research and contributed new reagents or analytic tools. YZ and MR analyzed the data. YZ and XZ wrote the manuscript. Funding This work was supported by the National Natural Science Foundation of China (81703149). Conflict of Interest Statement The authors declare that the research was conducted in the absence of any commercial or financial relationsh...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research