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Prevailing Effects of Ibutilide on Fast Delayed Rectifier K+ Channel

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The Journal of Membrane Biology Aims and scope Submit manuscript

… results argue against the presence of an inductive element having a constant value but favor the suggestion that the apparent inductance has the nature

of ‘delayed rectification’…(Weidmann 1950).

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-tail/ΔIK 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.

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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

I K :

Delayed rectifier potassium currents

I K-tail :

Delayed rectifier potassium currents upon repolarization

I Kr :

Rapid component of delayed rectifier potassium currents

I Ks :

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

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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.

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Authors and Affiliations

  1. Department of Cardiology, University Hospital Heidelberg, 69120, Heidelberg, Germany

    Sodikdjon A. Kodirov, Vladimir L. Zhuravlev & Johannes Brachmann

  2. Department of Physiology, Saint Petersburg University, Saint Petersburg, Russia, 199034

    Sodikdjon A. Kodirov & Vladimir L. Zhuravlev

  3. Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteura St., 02-093, Warsaw, Poland

    Sodikdjon A. Kodirov

  4. Department of Cardiology, Klinikum Coburg, Teaching Hospital of the University of Würzburg, Coburg, Germany

    Sodikdjon A. Kodirov & Johannes Brachmann

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  1. Sodikdjon A. Kodirov
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  2. Vladimir L. Zhuravlev
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Correspondence to Sodikdjon A. Kodirov.

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Kodirov, S.A., Zhuravlev, V.L. & Brachmann, J. Prevailing Effects of Ibutilide on Fast Delayed Rectifier K+ Channel. J Membrane Biol 252, 609–616 (2019). https://doi.org/10.1007/s00232-019-00098-x

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  • DOI: https://doi.org/10.1007/s00232-019-00098-x

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