Action potential clamp fingerprints of K+ currents in canine cardiomyocytes:: their role in ventricular repolarization

Aim: The aim of the present study was to give a parametric description of the most important K+ currents flowing during canine ventricular action potential. Methods: Inward rectifier K+ current (I-K1), rapid delayed rectifier K+ current (I-Kr), and transient outward K+ current (I-to) were dissected under action potential clamp conditions using BaCl2, E-4031, and 4-aminopyridine, respectively. Results: The maximum amplitude of I-to was 3.0 +/- 0.23 pA/pF and its integral was 29.7 +/- 2.5 fC/pF. The current peaked 4.4 +/- 0.7 ms after the action potential upstroke and rapidly decayed to zero with a time constant of 7.4 +/- 0.6 ms. I-Kr gradually increased during the plateau, peaked 7 ms before the time of maximum rate of repolarization (V-max(-)) at -54.2 +/- 1.7 mV, had peak amplitude of 0.62 +/- 0.08 pA/pF, and integral of 57.6 +/- 6.7 fC/pF. I-K1 began to rise from -22.4 +/- 0.8 mV, peaked 1 ms after the time of V-max(-) at -58.3 +/- 0.6 mV, had peak amplitude of 1.8 +/- 0.1 pA/pF, and integral of 61.6 +/- 6.2 fC/pF. Good correlation was observed between peak I-K1 and V-max(-). Neither I-K1 nor I-Kr was frequency-dependent between 0.2 and 1.66 Hz. Congruently, I-Kr failed to accumulate in canine myocytes at fast driving rates. Conclusions: Terminal repolarization is dominated by I-K1, but action potential duration is influenced by several ion currents simultaneously. As I-to was not active during the plateau, and neither I-K1 nor I-Kr was frequency-dependent, other currents must be responsible for the frequency dependence of action potential duration at normal and slow heart rates in canine ventricular cells.