Ca2+ channel inhibitor NNC 55-0396 inhibits voltage-dependent K+ channels in rabbit coronary arterial smooth muscle cells

J Pharmacol Sci. 2014;125(3):312-9. doi: 10.1254/jphs.14054fp. Epub 2014 Jul 1.

Abstract

We demonstrated the inhibitory effect of NNC 55-0396, a T-type Ca(2+) channel inhibitor, on voltage-dependent K(+) (K(V)) channels in freshly isolated rabbit coronary arterial smooth muscle cells. NNC 55-0396 decreased the amplitude of K(V) currents in a concentration-dependent manner, with an IC(50) of 0.080 μM and a Hill coefficient of 0.76.NNC 55-0396 did not affect steady-state activation and inactivation curves, indicating that the compound does not affect the voltage sensitivity of K(V) channel gating. Both the K(V) currents and the inhibitory effect of NNC 55-0396 on K(V) channels were not altered by depletion of extracellular Ca(2+) or intracellular ATP, suggesting that the inhibitory effect of NNC 55-0396 is independent of Ca(2+)-channel activity and phosphorylation-dependent signaling cascades. From these results, we concluded that NNC 55-0396 dosedependently inhibits K(V) currents, independently of Ca(2+)-channel activity and intracellular signaling cascades.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzimidazoles / pharmacology*
  • Calcium Channel Blockers / pharmacology*
  • Calcium Channels, T-Type / drug effects*
  • Calcium Channels, T-Type / physiology
  • Calcium Signaling
  • Cells, Cultured
  • Coronary Vessels / cytology*
  • Cyclopropanes / pharmacology*
  • Dose-Response Relationship, Drug
  • Muscle, Smooth, Vascular / cytology*
  • Muscle, Smooth, Vascular / drug effects*
  • Naphthalenes / pharmacology*
  • Phosphorylation
  • Potassium Channels, Voltage-Gated / antagonists & inhibitors*
  • Potassium Channels, Voltage-Gated / physiology
  • Rabbits

Substances

  • Benzimidazoles
  • Calcium Channel Blockers
  • Calcium Channels, T-Type
  • Cyclopropanes
  • Naphthalenes
  • Potassium Channels, Voltage-Gated
  • NNC 55-0396