Prevailing Effects of Ibutilide on Fast Delayed Rectifier K+ Channel
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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.
KeywordsTail current Antiarrhythmic agents HERG
Action potential duration
Action potential duration at 90% repolarization
Voltage-dependent calcium channel responsible for L-type currents
Delayed rectifier potassium currents
Delayed rectifier potassium currents upon repolarization
Rapid component of delayed rectifier potassium currents
Slow component of delayed rectifier potassium currents
Maximum diastolic potential, the counterpart of RMP in pacemaker cells
Duration of PR waves reflects the electrical conductance from atria to ventricle
Timing of QRS complex reflects the depolarization phase of ventricular AP
Interval between the Q and T waves in ECG
Resting membrane potential
Torsades de Pointes
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.
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.
The guidelines for the care and use of laboratory animals were strictly followed, and all procedures were approved by the local committee.