Pharmacology of ATP-sensitive K+ currents in smooth muscle cells from rabbit mesenteric artery

Am J Physiol. 1995 Nov;269(5 Pt 1):C1112-8. doi: 10.1152/ajpcell.1995.269.5.C1112.


The inference that ATP-sensitive K+ (KATP) channels are involved in arterial responses to the synthetic K+ channel openers, hypoxia, adenosine, and calcitonin gene-related peptide, has relied on the sensitivity of these responses to the sulfonylureas glibenclamide and tolbutamide and to tetraethylammonium (TEA+). The inhibition of KATP currents by glibenclamide, tolbutamide, and TEA+ was investigated in single smooth muscle cells from rabbit mesenteric artery by use of the whole cell patch-clamp technique. The synthetic K+ channel openers pinacidil (half-activation 0.6 microM), cromakalim (half-activation 1.9 microM), and diazoxide (half-activation 37.1 microM) activated K(+)-selective currents that were blocked by glibenclamide. Elevation of pipette (intracellular) ATP concentration decreased K+ currents induced by pinacidil. Half-inhibition of KATP currents by glibenclamide and tolbutamide occurred at 101 nM and 351 microM, respectively. KATP currents were also inhibited by external TEA+, with half-inhibition at 6.2 mM. The results indicate that glibenclamide is an effective inhibitor of KATP channels in arterial smooth muscle and that tolbutamide and TEA+ are much less effective. Furthermore, these results support numerous functional studies that have demonstrated that the vasorelaxations to K+ channel openers are inhibited by < 10 microM glibenclamide but not by < 1 mM TEA+.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Triphosphate / pharmacology*
  • Animals
  • Cells, Cultured
  • Electric Conductivity
  • Glyburide / pharmacology
  • Mesenteric Arteries / cytology
  • Mesenteric Arteries / metabolism*
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / metabolism*
  • Potassium Channel Blockers
  • Potassium Channels / drug effects
  • Potassium Channels / physiology*
  • Rabbits
  • Sulfonylurea Compounds / pharmacology
  • Tetraethylammonium
  • Tetraethylammonium Compounds / pharmacology
  • Vasodilator Agents / pharmacology


  • Potassium Channel Blockers
  • Potassium Channels
  • Sulfonylurea Compounds
  • Tetraethylammonium Compounds
  • Vasodilator Agents
  • Tetraethylammonium
  • Adenosine Triphosphate
  • Glyburide