Hyperpolarization of isolated capillaries from guinea-pig heart induced by K+ channel openers and glucose deprivation.
1. The present study was designed to test if microvascular coronary endothelial cells express ATP-sensitive K+ channels (KATP channels). We performed microfluorometric measurements of the membrane potential of freshly isolated guinea-pig coronary capillaries equilibrated with the voltage-sensitive dye bis-oxonol (bis-[1,3-dibutylbarbituric acid] trimethineoxonol, [DiBAC4(3)]). 2. The resting membrane potential of capillaries in physiological salt solution was -46 +/- 4.2 mV (n = 8) at room temperature (22 degrees C) as determined after calibration of the fluorescence using the Na(+)-K+ ionophore gramicidin in the presence of different K+ concentrations. Spontaneous membrane potential fluctuations of 10-20 mV amplitude were often observed. 3. A reversible, sustained hyperpolarization to a new membrane potential close to the K+ equilibrium potential (EK) could be induced by application of the K+ channel openers HOE 234 (100 nM to 1 microM), diazoxide (10 PM to 100 nM) or pinacidil (100 nM). Subsequent addition of glibenclamide (200 nM to 2 microM) reversed this hyperpolarization. 4. A glibenclamide-sensitive hyperpolarization of coronary capillaries to values near EK was also observed upon omission of D-glucose (10 mM) from the superfusing solution or by substituting L-glucose for D-glucose. Maximum hyperpolarization was reached in less than 10 min. 5. Our results suggest that microvascular coronary endothelial cells express KATP channels which may be activated during hypoglycaemia.
Langheinrich
U
U
Institute of Physiology, University of Marburg, Germany. langhein@mailer.uni-marburg.de
Daut
J
J
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001463:Barbiturates; D002196:Capillaries / Q000187:drug effects / Q000502:physiology*; D002839:Chromans / Q000494:pharmacology*; D003326:Coronary Circulation / Q000502:physiology*; D003981:Diazoxide / Q000494:pharmacology*; D005456:Fluorescent Dyes; D005947:Glucose / Q000494:pharmacology*; D005905:Glyburide / Q000494:pharmacology; D006096:Gramicidin / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007555:Isoxazoles; D008564:Membrane Potentials / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009994:Osmolar Concentration; D020110:Pinacidil; D011188:Potassium / Q000494:pharmacology; D015221:Potassium Channels / Q000819:agonists*; D011759:Pyrrolidines / Q000494:pharmacology*; D012965:Sodium Chloride; D014665:Vasodilator Agents / Q000494:pharmacology
D001463:Barbiturates; D002839:Chromans; D005456:Fluorescent Dyes; D006146:Guanidines; D007555:Isoxazoles; D015221:Potassium Channels; D011759:Pyrrolidines; D014665:Vasodilator Agents; C052795:bis(1,3-dibutylbarbiturate)trimethine oxonol; D006096:Gramicidin; D012965:Sodium Chloride; C075012:rilmakalim; D020110:Pinacidil; D000255:Adenosine Triphosphate; D005947:Glucose; D003981:Diazoxide; D011188:Potassium; D005905:Glyburide