ATP-sensitive K+ channels in rat aorta and brain microvascular endothelial cells

Am J Physiol. 1993 Sep;265(3 Pt 1):C812-21. doi: 10.1152/ajpcell.1993.265.3.C812.

Abstract

The endothelium plays an important role in the modulation of vascular tone and blood cell activation. Extensive work has demonstrated that the release of endothelium-derived relaxing factor (EDRF) from the endothelium is evoked by a number of physical and chemical stimuli requiring Ca2+. Because endothelial cells do not express voltage-dependent Ca2+ channels, Ca2+ influxes following receptor activation may be facilitated by cell hyperpolarizations mediated by the activation of K+ conductances. There has been recent interest in the role of ATP-sensitive K+ channels (KATP) suggesting that KATP may play a role in the regulation of blood flow. We have investigated the electrophysiological properties of an ATP-sensitive K+ conductance in whole cell and membrane patches from rat aorta and brain microvascular endothelial cells. Whole cell as well as single-channel currents were increased by either intracellular dialysis of ATP or application of glucose-free/NaCN (2 mM) solutions. Both currents were reversibly blocked by glibenclamide (1-100 microM). The KATP channel opener pinacidil (30 microM) caused activation of an outward current in the presence of physiological intracellular ATP concentrations. In inside-out patches, 10 microM-1 mM ATP invariably caused a dramatic decrease in channel activity. We conclude that both rat aorta and brain microvascular endothelial cells express KATP channels. KATP may play a role in the regulation of endothelial cell resting potential during impaired energy supply and therefore modulate EDRF release and thus cerebral blood flow.

Publication types

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

MeSH terms

  • Adenosine Triphosphate / pharmacology*
  • Animals
  • Aorta / cytology
  • Aorta / metabolism*
  • Cell-Free System / metabolism
  • Cells, Cultured
  • Cerebrovascular Circulation*
  • Electrophysiology
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / metabolism*
  • Guanidines / pharmacology
  • Microcirculation
  • Pinacidil
  • Potassium Channels / drug effects*
  • Potassium Channels / metabolism*
  • Potassium Channels / physiology
  • Rats

Substances

  • Guanidines
  • Potassium Channels
  • Pinacidil
  • Adenosine Triphosphate