Effects of carvedilol on transient outward and ultra-rapid delayed rectifier potassium currents in human atrial myocytes

Life Sci. 2007 Jan 23;80(7):665-71. doi: 10.1016/j.lfs.2006.10.012. Epub 2006 Nov 10.

Abstract

Carvedilol is a beta- and alpha(1)-adrenoceptor antagonist. It is widely used in the treatment of cardiovascular diseases including atrial arrhythmias. However, it is unclear whether carvedilol may affect the repolarization currents, transient outward K(+) current (I(to)) and ultra-rapid delayed rectifier K(+) current (I(Kur)) in the human atrium. The present study evaluated effects of carvedilol on I(to) and I(Kur) in isolated human atrial myocytes by whole-cell patch-clamp recording technique. We found that carvedilol reversibly inhibited I(to) and I(Kur) in a concentration-dependent manner. Carvedilol (0.3 microM) suppressed I(to) from 9.2+/-0.5 pA/pF to 4.8+/-0.5 pA/pF (P<0.01) and I(Kur) from 3.6+/-0.5 pA/pF to 1.9+/-0.3 pA/pF (P<0.01) at +50 mV. I(to) was inhibited in a voltage-dependent manner, being significantly attenuated at test potentials from +10 to +50 mV, whereas the inhibition of I(Kur) was independent. The concentration giving a 50% inhibition was 0.50 microM for I(to) and 0.39 microM for I(Kur). Voltage-dependence of activation, inactivation and time-dependent recovery from inactivation of I(to) were not altered by carvedilol. However, time to peak and time-dependent inactivation of I(to) were significantly accelerated, indicating an open channel blocking action. The findings indicate that carvedilol significantly inhibits the major repolarization K(+) currents I(to) and I(Kur) in human atrial myocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-Antagonists / pharmacology*
  • Adrenergic beta-Antagonists / pharmacology*
  • Adult
  • Aged
  • Carbazoles / pharmacology*
  • Carvedilol
  • Delayed Rectifier Potassium Channels / drug effects*
  • Dose-Response Relationship, Drug
  • Heart Atria / drug effects
  • Heart Atria / pathology
  • Humans
  • Middle Aged
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / pathology
  • Myocytes, Cardiac / physiology
  • Patch-Clamp Techniques
  • Potassium Channel Blockers / pharmacology*
  • Propanolamines / pharmacology*
  • Time Factors

Substances

  • Adrenergic alpha-Antagonists
  • Adrenergic beta-Antagonists
  • Carbazoles
  • Delayed Rectifier Potassium Channels
  • Potassium Channel Blockers
  • Propanolamines
  • Carvedilol