Article

Contribution of IKr and IK1 to ventricular repolarization in canine and human myocytes: is there any influence of action potential duration?

Hungarian Academy of Sciences Division of Cardiovascular Pharmacology Szeged Hungary
Archiv für Kreislaufforschung (Impact Factor: 7.35). 04/2009; 104(1):33-41. DOI: 10.1007/s00395-008-0730-3

ABSTRACT BackgroundThe aim of the present work was to study the profile of the rapid delayed rectifier potassium current (IKr) and the inward rectifier potassium current (IK1) during ventricular repolarization as a function of action potential duration and rate of repolarization.
MethodsWhole cell configuration of the patch clamp technique was used to monitor IKr and IK1 during the action potential plateau and terminal repolarization. Action potentials recorded at various cycle lengths (0.4–5s) and repolarizing voltage ramps having various slopes (0.5–3V/s) were used as command signals. IKr and IK1 were identified as difference currents dissected by E-4031 and BaCl2, respectively.
ResultsNeither peak amplitudes nor mean values of IKr and IK1 recorded during the plateau of canine action potentials were influenced by action potential duration. The membrane potential where IKr and IK1 peaked during the terminal repolarization was also independent of action potential duration. Similar esults were obtained in undiseased human ventricular myocytes, and also in canine cells when IKr and IK1 were evoked using repolarizing voltage ramps of various slopes. Action potential voltage clamp experiments revealed that the peak values of IKr, IK1, and net outward current during the terminal repolarization were independent of the pacing cycle length within the range of 0.4 and 5s.
ConclusionsThe results indicate that action potential configuration fails to influence the amplitude of IKr and IK1 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 IKr or IK1 kinetics in these species.

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