ATP-sensitive K+ channels in rat aorta and brain microvascular endothelial cells.
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.
Janigro
D
D
Department of Neurological Surgery, University of Washington, Seattle 98104.
West
G A
GA
Gordon
E L
EL
Winn
H R
HR
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000378:metabolism*; D002474:Cell-Free System / Q000378:metabolism; D002478:Cells, Cultured; D002560:Cerebrovascular Circulation; D004594:Electrophysiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006146:Guanidines / Q000494:pharmacology; D008833:Microcirculation; D020110:Pinacidil; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D051381:Rats
D006146:Guanidines; D015221:Potassium Channels; D020110:Pinacidil; D000255:Adenosine Triphosphate