Effects of the chromanol 293B, a selective blocker of the slow, component of the delayed rectifier Kq current on repolerisation in human and guinea pig ventricular myocytes

  • Bosch R
  • Gaspo R
  • Busch A
 et al. 
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Objectives: The slow component of the delayed rectifier K current I is believed to be important in cardiac repolarization, and q Ž. Ks 368C. Results: Delayed rectifier current I elicited by pulses toq60 mV from a holding potential ofy50 mV in guinea pig myocytes Ž may be a potential target for antiarrhythmic drugs, but its study has been limited by a lack of specific blockers. The chromanol derivate 293B blocks currents expressed by minK and not HERG in Xenopus oocytes, but little is known about its effects on native currents and action potentials. We aimed to establish the effects of 293B on Kq,Naq and Ca2q currents and action potentials in human and guinea pig cardiomyocytes. Methods: Whole-cell patch clamp techniques were applied to assess the effects of 293B on isolated myocytes at Ž. K was strongly inhibited by 293B maximum inhibition 96.9"0.8%; 50% inhibitory concentration, EC , 1.02 mM., but I during pulses to Ž.y10 mV was unaffected 3.9"8.4% inhibition at 50 mM . Half-activation voltages, current-voltage relations, and current densities of drug-resistant and drug-sensitive I correspond to those of I and I respectively. Inward rectifier Kq current, Naq current and L-type 50 Ca2q current were unaffected by 293B. Transient outward current in human ventricular myocytes was inhibited by 293B at an EC of 2450 mM, less than one twentieth the potency for I inhibition in guinea pig myocytes. While dofetilide prolonged action potential duration Ž. KKr Ks APD with strong reverse use dependence, 293B prolonged guinea pig and human ventricular APD to a similar fractional extent at all frequencies. Conclusions: 293B is a selective I blocker, and the frequency dependence of APD prolongation caused by this I blocker is different from that caused by I blockade: 293B may be an interesting tool to study the physiologic role of I and the antiarrhythmic potential of I blockade. q1998 Elsevier Science B.V. All rights reserved. Ks Kr Ks Keywords: Potassium channels; Action potential; Biophysics; Cardiac arrhythmias; Ant

Author-supplied keywords

  • 1998
  • 293b
  • 441
  • 450
  • a selective blocker of
  • component of the delayed
  • diovascular research 38 ž
  • effects of the chromanol
  • human and guinea pig
  • on repolarization in
  • rectifier k q current
  • the slow
  • ventricular myocytes

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  • Ralph F Bosch

  • Rania Gaspo

  • Andreas E Busch

  • Hans J Lang

  • Gui-rong Li

  • Stanley Nattel

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