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

• Published in: Acta Physiologica 2007-07, Vol.190 (3), p.189-198
• Main Authors: Bányász, T, Magyar, J, Szentandrássy, N, Horváth, B, Birinyi, P, Szentmiklósi, J, Nánási, P.P
• Format: Article
• Language: English
• Subjects: action potential clamp; action potential duration; Action Potentials - physiology; Animals; Biological and medical sciences; Cells, Cultured; dog myocytes; Dogs; Electrophysiology; Female; frequency dependence; Fundamental and applied biological sciences. Psychology; Heart Ventricles - cytology; Male; Myocytes, Cardiac - metabolism; Patch-Clamp Techniques; Potassium - metabolism; Potassium Channels, Inwardly Rectifying - metabolism; potassium currents; Ventricular Function; ventricular repolarization; Vertebrates: anatomy and physiology, studies on body, several organs or systems
• ISSN: 1748-1708; 1748-1716
• DOI: 10.1111/j.1748-1716.2007.01674.x

The aim of the present study was to give a parametric description of the most important K⁺ currents flowing during canine ventricular action potential. 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. 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 [graphic removed] ) 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 [graphic removed] 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 [graphic removed] (r = 0.93) but none between IKr and V [graphic removed] . 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. 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.