Contribution of I Kr and I K1 to ventricular repolarization in canine and human myocytes: is there any influence of action potential duration?
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.
Jost
Norbert
N
Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary.
Acsai
Károly
K
Horváth
Balázs
B
Bányász
Tamás
T
Baczkó
István
I
Bitay
Miklós
M
Bogáts
Gábor
G
Nánási
Péter P
PP
D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D017609:Barium Compounds / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D004285:Dogs; D004594:Electrophysiology / Q000379:methods; D006801:Humans; D054086:KATP Channels / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D032342:Muscle Cells / Q000502:physiology*; D018408:Patch-Clamp Techniques; D024661:Potassium Channels, Inwardly Rectifying / Q000187:drug effects / Q000502:physiology*; D012016:Reference Values; D016276:Ventricular Function / Q000502:physiology*
D017609:Barium Compounds; D002712:Chlorides; D054086:KATP Channels; D024661:Potassium Channels, Inwardly Rectifying; C024986:barium chloride