The Effects of the Selective Serotonin Reuptake Inhibitor Fluvoxamine on Voltage-Dependent K(+) Channels in Rabbit Coronary Arterial Smooth Muscle Cells

Biol Pharm Bull. 2015;38(8):1208-13. doi: 10.1248/bpb.b15-00207.

Abstract

We demonstrated the inhibitory effect of fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), on voltage-dependent K(+) (Kv) channels in freshly isolated rabbit coronary arterial smooth muscle cells using a whole-cell patch clamp technique. Fluvoxamine reduced the amplitude of Kv currents in a concentration-dependent manner with an IC50 value of 3.71±1.09 µM and a Hill coefficient of 0.62±0.14. Although fluvoxamine did not significantly affect the steady-state activation curve, it shifted the steady-state inactivation curve toward a more negative potential. Pretreatment with another SSRI, paroxetine, did not affect the basal Kv current and did not alter the inhibitory effect of fluvoxamine on Kv channels. We concluded that fluvoxamine inhibits the Kv current in a concentration-dependent manner and in a closed (inactivated) state of the Kv channels independent of serotonin reuptake inhibition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Coronary Vessels / drug effects*
  • Coronary Vessels / metabolism
  • Dose-Response Relationship, Drug
  • Fluvoxamine / adverse effects
  • Fluvoxamine / pharmacology*
  • Male
  • Muscle, Smooth, Vascular / drug effects*
  • Muscle, Smooth, Vascular / metabolism
  • Myocytes, Smooth Muscle / drug effects*
  • Myocytes, Smooth Muscle / metabolism
  • Patch-Clamp Techniques
  • Potassium Channels, Voltage-Gated / metabolism*
  • Rabbits
  • Selective Serotonin Reuptake Inhibitors / adverse effects
  • Selective Serotonin Reuptake Inhibitors / pharmacology*

Substances

  • Potassium Channels, Voltage-Gated
  • Serotonin Uptake Inhibitors
  • Fluvoxamine