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 BaCl(2), 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)(-) (r = 0.93) but none between I(Kr) 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.

Conclusion: 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.