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The Journal of Membrane Biology

, Volume 252, Issue 6, pp 609–616 | Cite as

Prevailing Effects of Ibutilide on Fast Delayed Rectifier K+ Channel

  • Sodikdjon A. KodirovEmail author
  • Vladimir L. Zhuravlev
  • Johannes Brachmann
Article
  • 78 Downloads

Abstract

Effects of ibutilide, a class III antiarrhythmic drug, on delayed rectifier potassium currents (IK) in freshly isolated guinea pig ventricular myocytes were studied. Experiments were performed using the whole-cell configuration of patch-clamp technique under blockade of L-type calcium currents (Cav1). Ibutilide at concentrations ranging between 10 nM and 100 µM inhibited IKr in dose-dependent manner with a half maximal effective concentration of 2.03 ± 0.74 µM (n = 5–10). The amplitude of tail currents activated by prepulse to + 20 mV was decreased from 253 ± 52 to 130 ± 25 pA (n = 8, p < 0.01) in the presence of 1 µM ibutilide. The envelope test revealed time-dependent changes in ratio of IK-tailIK during 0.2–2 s pulse durations in the absence of drug. With ibutilide, regardless of pulse duration, a relatively constant ratio was estimated, indicative of predominant involvement of IKr component. The slow IKs persisted to greater extent even at 100 μM ibutilide revealing a distinguishable selectivity toward the IKr component.

Keywords

Tail current Antiarrhythmic agents HERG 

Abbreviations

AF

Atrial fibrillation

AP

Action potential

APD

Action potential duration

APD90

Action potential duration at 90% repolarization

Cav1

Voltage-dependent calcium channel responsible for L-type currents

EAD

Early afterdepolarization

ECG

Electrocardiogram

IK

Delayed rectifier potassium currents

IK-tail

Delayed rectifier potassium currents upon repolarization

IKr

Rapid component of delayed rectifier potassium currents

IKs

Slow component of delayed rectifier potassium currents

LV

Left ventricle

MDP

Maximum diastolic potential, the counterpart of RMP in pacemaker cells

PR

Duration of PR waves reflects the electrical conductance from atria to ventricle

QRS

Timing of QRS complex reflects the depolarization phase of ventricular AP

QT

Interval between the Q and T waves in ECG

RMP

Resting membrane potential

RV

Right ventricle

TdP

Torsades de Pointes

Notes

Acknowledgements

Technical support of Mrs. Klara Güth and comments and useful discussions by Drs. Armin Just and Johannes Vogel, Heidelberg University are gratefully acknowledged. We thank Mrs. Tania Simon, Heidelberg University and Mrs. Carrie Couper, Harvard University for critically reading the manuscript.

Funding

Deutsche Forschungsgemeinschaft and SFB320 ‘Herzfunktion und ihre Regulation’ project.

Compliance with Ethical Standards

Conflict of interest

None of the Authors have potential conflicts of interest.

Ethical Approval

The guidelines for the care and use of laboratory animals were strictly followed, and all procedures were approved by the local committee.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Sodikdjon A. Kodirov
    • 1
    • 2
    • 3
    • 4
    Email author
  • Vladimir L. Zhuravlev
    • 1
    • 2
  • Johannes Brachmann
    • 1
    • 4
  1. 1.Department of CardiologyUniversity Hospital HeidelbergHeidelbergGermany
  2. 2.Department of PhysiologySaint Petersburg UniversitySaint PetersburgRussia
  3. 3.Nencki Institute of Experimental Biology, Polish Academy of SciencesWarsawPoland
  4. 4.Department of CardiologyKlinikum Coburg, Teaching Hospital of the University of WürzburgCoburgGermany

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