Biophysical characterization of inwardly rectifying potassium currents (IK1, IK,Ach, IK,Ca) using sinus rhythm or atrial fibrillation action potential waveforms

Although several physiological, pathophysiological and regulatory properties of classical inward rectifier K+ current I-K1, G-protein coupled inwardly-rectifying K+ current I-K,I-Ach and the small-conductance Ca2+ activated K+ current I-K,I-Ca have been identified, quantitative biophysical details remain unclear. Both I-K1 and I-K,I-ACh are implicated in atrial fibrillation (AF), and recently also I-K,I-Ca has been speculated to be linked with the genesis and sustainability of AF. All these three currents have been shown to be involved in the electrical remodeling in the atria of patients suffering from AF, and it is therefore important to characterize their biophysical properties and compare their relative current contribution in atrial electrophysiology in both sinus rhythm (SR) and AF. The aim of this study is to investigate the contribution of the three potassium currents when subjected to voltage protocols adapted from atrial action potentials recorded in human tissue at 1 and 3 Hz. The current recordings were performed in the HEK-293 heterologous cell system expressing either I-K1, I-K,I-ACh or I-K,I-Ca to establish the individual contribution of each of these currents during the voltage changes of atrial action potential waveforms. I-K1 primarily contributes to the atrial electrophysiology at the latter part of repolarization and during the diastolic phase, while both I-K,I-Ca under high [Ca2+](i) and I-K,I-Ach contribute relatively most during repolarization.