Abstract
Interactions between antiarrhythmic drugs and ion channels are important subjects in the field of cardiovascular electro-pharmacology. This study explores the relationship between propafenone and C-type inactivation of Kv1.4 channel. fKv1.4ΔN, a ferret Kv1.4 N-terminal delected mutant, was employed in this study. fKv1.4ΔN cRNA was injected intoXenopus oocytes to express fKv1.4ΔN channel and two electrode voltage clamp technique was used to record the current. We found that fKv1.4ΔN channel current was rapidly depressed in a frequency-dependent manner and meanwhile, C-type inactivation in this channel was increased more than 7 folds in the presence of 100 μM propafenone. While propafenone has no effect on Kv1.4ΔN recovery. All the results indicate that propafenone blocks Kv1.4ΔN channel through intracellular bindings and that binding of propafenone with Kv1.4ΔN channel leads to a conformational change on the extracellular site which accelerates C-type inactivation, suggesting that propafenone, as an open channel blocker, may affect the mechanism of C-type inactivation.
Resumen
Las interacciones entre los fármacos antiarrítmicos y los canales iónicos son temas importantes en el campo de la electrofarmacología cardiovascular. Se estudia en este trabajo la relación entre la propafenona y la incativación de tipo C del canal Kv1.4. Se ha utilizado fKv1.4Φ N, un mutante con una delección en el extremo amino terminal.
Se inyectaba en oocitos deXenopus laevis cRNA de f Kv1.4ΦN para expresar el canal fKv1.4ΦN y se registraba la corriente mediante ténicas electrofisiológicas. La corriente del canal f Kv1.4ΦN disminuye rápidamente de manera dependiente de la frecuencia y meintras tanto, la inactivación de tipo C en el canal aumentaba mas de 7 veces en presencia de propafenona 100 μM. En cambio, la propafenona no afecta a la recuperación del canal. Los resultados indican que la propafenona bloquea el canal Kv1.4ΦN mediante uniones intracelulares que determinan un camio conformacional en el lado extracelular que acelera la inactivación de tipo C.
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Tian, L., Jiang, X., Rasmusson, R. et al. Effect of propafenone on Kv1.4 inactivation. J. Physiol. Biochem. 62, 263–270 (2006). https://doi.org/10.1007/BF03165755
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DOI: https://doi.org/10.1007/BF03165755