Species-dependent differences in the inhibition of various potassium currents and in their effects on repolarization in cardiac ventricular muscle

• DOI: 10.1139/cjpp-2022-0028
• Publication Date: 2022-04-20T17:08:31Z
• Authors: Tamás Árpádffy-Lovas; Aiman Saleh A. Mo...; Muhammad Naveed; István Koncz; Beáta Baláti; Miklós Bitay; Norbert Jost; Norbert Nagy; István Baczkó; László Virág; András Varró
• Keywords: Dofetilide; Cardiac Electrophysiology; Potassium channel blocker

Even though rodents are accessible model animals, their electrophysiological properties deeply different from those of humans, making the translation rat studies to humans rather difficult. We compared mechanisms ventricular repolarization in various animal models by measuring cardiac action potentials papillary muscle preparations using conventional microelectrodes and applying selective inhibitors potassium transmembrane ion currents. Inhibition IK1 current (10 µmol/L barium chloride) significantly prolonged repolarization, but only slightly it dogs, did not affect humans. On contrary, IKr inhibition (50 nmol/L dofetilide) rabbits, rats. IKur (1 XEN-D0101) had no effect or dogs. IKs (500 HMR-1556) Ito currents (100 chromanol-293B) elicited similar effects all investigated species. conclude that dog have strongest translational value weakest experiments.