The class III anti-arrhythmic agent, amiodarone, inhibits voltage-dependent K(+) channels in rabbit coronary arterial smooth muscle cells

Naunyn Schmiedebergs Arch Pharmacol. 2016 Jul;389(7):713-21. doi: 10.1007/s00210-016-1232-8. Epub 2016 Mar 31.

Abstract

We examined the inhibitory effect of amiodarone, a class III anti-arrhythmic agent, on voltage-dependent K(+) (Kv) currents in freshly isolated rabbit coronary arterial smooth muscle cells, using a whole-cell patch clamp technique. Amiodarone inhibited Kv currents in a concentration-dependent manner, with a half-maximal inhibitory concentration (IC50) value of 3.9 ± 1.44 μM and a Hill coefficient of 0.45 ± 0.14. Amiodarone did not have a significant effect on the steady-state activation of Kv channels, but shifted the inactivation current toward a more negative potential. Application of consecutive pulses progressively augmented the amiodarone-induced Kv channel inhibition. Another class III anti-arrhythmic agent, dofetilide, did not inhibit the Kv current or change the inhibitory effect of amiodarone on Kv channels. Therefore, these results strongly suggest that amiodarone inhibits Kv currents in a concentration- and state-dependent manner.

Keywords: Amiodarone; Coronary artery; Voltage-dependent K+ channel.

MeSH terms

  • Amiodarone / pharmacology*
  • Animals
  • Anti-Arrhythmia Agents / pharmacology*
  • Coronary Vessels / drug effects
  • Coronary Vessels / metabolism
  • Dose-Response Relationship, Drug
  • Ion Channel Gating / drug effects
  • Kv1.5 Potassium Channel / antagonists & inhibitors
  • Kv1.5 Potassium Channel / metabolism
  • Male
  • Membrane Potentials
  • Muscle, Smooth, Vascular / drug effects*
  • Muscle, Smooth, Vascular / metabolism
  • Myocytes, Smooth Muscle / drug effects*
  • Myocytes, Smooth Muscle / metabolism
  • Patch-Clamp Techniques
  • Potassium Channel Blockers / pharmacology*
  • Potassium Channels, Voltage-Gated / antagonists & inhibitors*
  • Potassium Channels, Voltage-Gated / metabolism
  • Rabbits

Substances

  • Anti-Arrhythmia Agents
  • Kv1.5 Potassium Channel
  • Potassium Channel Blockers
  • Potassium Channels, Voltage-Gated
  • Amiodarone