An ATP‐sensitive potassium conductance in rabbit arterial endothelial cells.

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Abstract
1. Whole‐cell patch clamp recording was used to study an ATP‐sensitive, sulphonylurea‐inhibitable potassium (K+) conductance in freshly dissociated endothelial cells from rabbit arteries. 2. The ATP‐sensitive K+ conductance was activated by micromolar concentrations of the K+ channel opener, levcromakalim, and by metabolic inhibition of endothelial cells using dinitrophenol and iodoacetic acid. The current‐voltage (I‐V) relationship obtained in isotonic K+ solutions was linear between ‐150 and ‐50 mV and had a slope conductance of approximately 1 nS. 3. The permeability of the ATP‐sensitive K+ conductance determined from reversal potential measurements exhibited the following ionic selectivity sequence: Rb+ > K+ > Cs+ >> Na+ > NH4+ > Li+. 4. Membrane currents activated by either levcromakalim or metabolic inhibition were inhibited by the sulphonylurea drugs, glibenclamide and tolbutamide, with half‐maximal inhibitory concentrations of 43 nM and 224 microM and Hill coefficients of 1.1 and 1.2, respectively. Levcromakalim‐induced currents were also inhibited by millimolar concentrations of Ba2+ or tetraethylammonium ions in the external solution. 5. Levcromakalim (3 microM) and metabolic inhibition hyperpolarized endothelial cells by approximately 10‐15 mV in normal physiological salt solutions. The hyperpolarization induced by levcromakalim or metabolic inhibition was inhibited by bath application of 10 microM glibenclamide. 6. Internal perfusion of the cytosol of whole‐cell voltage‐clamped endothelial cells with an ATP‐free pipette solution activated a membrane current which was reversibly inhibited by internal perfusion with a 3 mM MgATP pipette solution. This current was insensitive to other adenine and guanine nucleotides in the pipette solution. The inward current evoked in a nominally ATP‐free internal solution was further increased by bath application of levcromakalim. 7. Levcromakalim (25 microM) did not induce a change in the intracellular Ca2+ concentration of fura‐2‐loaded endothelial cells, whereas metabolic inhibition caused a slow and sustained increase in intracellular Ca2+ concentration, which was attenuated by 10 microM glibenclamide applied externally.(ABSTRACT TRUNCATED AT 400 WORDS)

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