Hyperpolarisation of rat mesenteric endothelial cells by ATP-sensitive K(+) channel openers.
Membrane potential responses of rat mesenteric endothelial cells were investigated in intact arteries using sharp electrodes. Levcromakalim, an activator of ATP-sensitive K(+) channels (K(ATP)) induced concentration-dependent hyperpolarisation of the endothelial cells, which was reversible by glibenclamide and ciclazindol, inhibitors of K(ATP). Another K(ATP) activator, diazoxide, also hyperpolarised the endothelial cells. Carbachol induced endothelial hyperpolarisation that was inhibited by combinations of apamin and charybdotoxin, but not Ba(2+) and ouabain. Prior stimulation with levcromakalim inhibited carbachol-induced responses, and this inhibitory effect was also sensitive to glibenclamide. 1, 3-dihydro-1-[2-hydroxy-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl) -2H-benzimidazol-2-one (NS 1619), an activator of large conductance, Ca(2+)-activated K(+) channels (BK(Ca)), induced only small hyperpolarisations of the endothelial cells. Preincubation of tissues with 18 alpha- or 18 beta-glycyrrhetinic acid, inhibitors of gap junction communication, increased the input resistance and depolarised the endothelial cells, and inhibited the hyperpolarising effect of levcromakalim. It is concluded that activation of K(ATP) causes hyperpolarisation of rat mesenteric endothelial cells, probably through gap junctional transfer of smooth muscle hyperpolarisation, and that this may represent an important modulator of endothelial function.
White
R
R
Department of Pharmacology, University of Cambridge, Tennis Court Road, CB2 1QJ, Cambridge, UK.
Hiley
C R
CR
D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D017609:Barium Compounds / Q000494:pharmacology; D001562:Benzimidazoles / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D018999:Charybdotoxin / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D019806:Cromakalim / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D005905:Glyburide / Q000494:pharmacology; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008638:Mesenteric Arteries / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000494:pharmacology*
D017609:Barium Compounds; D001562:Benzimidazoles; D002712:Chlorides; D015221:Potassium Channels; D014665:Vasodilator Agents; D019806:Cromakalim; C024986:barium chloride; D018999:Charybdotoxin; C119129:18alpha-glycyrrhetinic acid; C086491:NS 1619; D001030:Apamin; D010042:Ouabain; D000255:Adenosine Triphosphate; D002217:Carbachol; D006034:Glycyrrhetinic Acid; D005905:Glyburide; D019331:NG-Nitroarginine Methyl Ester