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Action potential clamp fingerprints of K+ currents in canine cardiomyocytes: their role in ventricular repolarization.
Banyasz, T. 1; Magyar, J. 1; Szentandrassy, N. 1; Horvath, B. 1; Birinyi, P. 1; Szentmiklosi, J. 2; Nanasi, P. P. 1
[Miscellaneous Article] Acta Physiologica. 190(3):189-198, July 2007.

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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 (IK1), rapid delayed rectifier K current (IKr), and transient outward K current (Ito) were dissected under action potential clamp conditions using BaCl2, E-4031, and 4-aminopyridine, respectively.

Results: The maximum amplitude of Ito 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. IKr 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. IK1 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 IK1 and V-max (r = 0.93) but none between IKr and V-max. Neither IK1 nor IKr was frequency-dependent between 0.2 and 1.66 Hz. Congruently, IKr failed to accumulate in canine myocytes at fast driving rates.

Conclusion: Terminal repolarization is dominated by IK1, but action potential duration is influenced by several ion currents simultaneously. As Ito was not active during the plateau, and neither IK1 nor IKr 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.