Characterization of changes in the configuration of action potentials in the mouse, guinea pig, and pig sinoauricular node after application of channel blockers of the rapid and slow delayed rectifier potassium currents

Abstract

We hypothesized that the repolarization phase of action potentials (APs) in mammals with large body mass and high cardiac output could not be reliably controlled by only one of the delayed rectifier potassium I_K current components. To test this hypothesis experimentally, we performed a comparative study of the response of AP phases to the rapid I_Kr channels blocker E-4031 and slow I_Ks blocker chromanol 293B in APs spontaneously generated in strips of sinoauricular (SA) tissue from mouse, guinea pig, and pig hearts. Application of a slow channels blocker chromanol 293B caused a decrease of Aps generation frequency in SA area strips from mouse, guinea-pig and pig by 5.3, 16, and 18% compared to the control. Treatment with the I_Kr blocker E-4031 caused a significant reduction of APs generation frequency in the mouse, guinea pig, and pig SA strips by 24, 26, and 36%, respectively, compared to the control values. These results suggest that the rapid I_Kr current is the key component responsible for AP generation in sinoauricular node cells of the pig heart.