Dual modulation of swelling-activated chloride current by NO and NO donors in rabbit portal vein myocytes

• Published in: The Journal of physiology Vol. 528; no. 1; pp. 15 - 24
• Main Authors: Ellershaw, D. C., Greenwood, I. A., Large, W. A.
• Format: Journal Article
• Language: English
• Published: Oxford, UK The Physiological Society 01.10.2000; Blackwell Publishing Ltd; Blackwell Science Inc
• Subjects: Animals; Cell Size - drug effects; Cell Size - physiology; Cells, Cultured; Chelating Agents - pharmacology; Chloride Channels - drug effects; Chloride Channels - metabolism; Cyclic GMP - analogs & derivatives; Cyclic GMP - pharmacology; Cyclic GMP-Dependent Protein Kinases - antagonists & inhibitors; Cyclic GMP-Dependent Protein Kinases - metabolism; Guanylate Cyclase - antagonists & inhibitors; In Vitro Techniques; Meglumine - metabolism; Meglumine - pharmacology; Membrane Potentials - drug effects; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - metabolism; Nitric Oxide - metabolism; Nitric Oxide - pharmacology; Nitric Oxide Donors - metabolism; Nitric Oxide Donors - pharmacology; Original; Patch-Clamp Techniques; Penicillamine - analogs & derivatives; Penicillamine - pharmacology; Portal Vein - cytology; Portal Vein - metabolism; Rabbits; S-Nitroso-N-Acetylpenicillamine; Sodium - metabolism
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1111/j.1469-7793.2000.00015.x

The effects of authentic NO and the NO donor S- nitroso- N- acetylpenicillamine (SNAP) on swelling-activated chloride currents ( I swell ) were investigated in freshly dispersed rabbit portal vein smooth muscle cells. I swell was recorded with the perforated patch configuration of the whole-cell patch clamp technique. In approximately 50 % of cells NO and SNAP inhibited the amplitude of I swell by about 45 % in a voltage-independent manner. I swell was also inhibited by an inhibitor of NO-sensitive guanylate cyclase (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and by KT5823, an inhibitor of cGMP-dependent protein kinase. In other cells both NO and SNAP enhanced I swell by about 40 % in a voltage-independent manner. A similar increase was produced by application of the cell-permeable cGMP analogue 8-bromo-guanosine 3′,5′-cyclic monophosphate (8-Br-cGMP). However, 8-Br-cGMP had no effect on current amplitude in cells pre-treated with KT5823. In contrast 8-Br-cGMP increased the amplitude of I swell in cells which had been pre-treated with ODQ. SNAP also modulated I swell recorded in the conventional whole-cell configuration with internal solutions containing 10 m m EGTA to rule out any contribution from Ca 2+ -activated Cl − currents. These data suggest that the amplitude of I swell can be enhanced by NO via a cGMP-dependent phosphorylation and inhibited by NO in a cGMP-independent manner.