Introduction The course of repolarization is set by the interplay between different voltage- and time-dependent cur- rents. The contribution of each current strictly depends on the relation between its kinetic properties and the voltage profile during the electrical cycle, which varies with heart rate. Accordingly, action potential duration (APD) is rate-dependent: APD lengthens when the cycle length increases. Rate- dependent kinetic properties of several ion currents, including the rapid delayed rectifier potassium current (I Kr ), were claimed to contribute to the Norbert Jost Ka ´roly Acsai Bala ´zs Horva ´th Tama ´s Ba ´nya ´sz Istva ´n Baczko ´ Miklo ´s Bitay Ga ´bor Boga ´ts Pe ´ter P. Na ´na ´si Contribution of I Kr and I K1 to ventricular repolarization in canine and human myocytes: is there any influence of action potential duration? Received: 17 January 2008 Returned for 1. Revision: 5 February 2008 1. Revision received: 11 April 2008 Returned for 2. Revision: 14 May 2008 2. Revision received: 15 May 2008 Accepted: 20 May 2008 Published online: 5 July 2008 j Abstract Background The aim of the present work was to study the profile of the rapid delayed rectifier potassium current (I Kr ) and the inward rectifier potassium current (I K1 ) during ventricular repolarization as a function of action potential duration and rate of repolarization. Methods Whole cell configuration of the patch clamp technique was used to monitor I Kr and I K1 during the action potential plateau and terminal repolarization. Action potentials recorded at various cycle lengths (0.4–5 s) and repolarizing voltage ramps having various slopes (0.5–3 V/s) were used as command signals. I Kr and I K1 were identified as difference currents dissected by E-4031 and BaCl 2 , respectively. Results Neither peak amplitudes nor mean values of I Kr and I K1 recorded during the plateau of canine action potentials were influenced by action potential duration. The membrane potential where I Kr and I K1 peaked during the terminal repolarization was also independent of action potential duration. Similar results were obtained in undiseased human ventricular myocytes, and also in canine cells when I Kr and I K1 were evoked using repolarizing voltage ramps of various slopes. Action potential voltage clamp experiments revealed that the peak values of I Kr , I K1 , and net outward current during the terminal repolarization were independent of the pacing cycle length within the range of 0.4 and 5 s. Conclusions The results indicate that action potential configuration fails to influence the amplitude of I Kr and I K1 during the ventricular action potential in dogs and humans, suggesting that rate-dependent changes in action potential duration are not likely related to rate-dependent alterations in I Kr or I K1 kinetics in these species. j Key words ventricular repolarization – action potential duration – rate dependence – potassium currents – dog myocytes – human myocytes – action potential clamp ORIGINAL CONTRIBUTION Basic Res Cardiol 104:33–41 (2009) DOI 10.1007/s00395-008-0730-3 BRC 730 N. Jost Æ K. Acsai Æ I. Baczko ´ Dept. of Pharmacology and Pharmacotherapy University of Szeged Szeged, Hungary N. Jost Æ K. Acsai Division of Cardiovascular Pharmacology Hungarian Academy of Sciences Szeged, Hungary B. Horva ´th Æ T. Ba ´nya ´sz Æ P.P. Na ´na ´si (&) Dept. of Physiology University of Debrecen Nagyerdei krt 98 4012 Debrecen, Hungary Tel.: +36-52/416-634 Fax: +36-52/432-289 E-Mail: nanasi@phys.dote.hu M. Bitay Æ G. Boga ´ts Dept. of Cardiac Surgery University of Szeged Szeged, Hungary