ATP-sensitive K+ channels in smooth muscle cells of guinea-pig mesenteric lymphatics: role in nitric oxide and beta-adrenoceptor agonist-induced hyperpolarizations.
1. Intracellular microelectrode recordings were performed to investigate the membrane K+ conductances involved in smooth muscle hyperpolarization of lymphatic vessels in the guinea-pig mesentery. 2. Nitric oxide (NO), released either by the endothelium after acetylcholine (ACh; 10 microM) stimulation or by sodium nitroprusside (SNP; 50-100 microM), hyperpolarized lymphatic smooth muscle. These responses were inhibited with the guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazole [4,3-a]quinoxalin-1-one (ODQ, 10 microM). 3. ACh and SNP-induced hyperpolarizations were inhibited (by about 90%) upon application of the ATP-sensitive K+(K(ATP)) channel blocker, glibenclamide (10 microM), or with 4-aminopyridine (2.5 mM), but were not affected by the Ca2+-activated K+ channels blocker, penitrem A (100 nM). 4. Hyperpolarization caused by the K+ channel opener, cromakalim (0.1-10 microM), isoprenaline (0.1 microM) or forskolin (0.5 microM) were all significantly blocked by glibenclamide. 5. Hyperpolarization evoked by ACh and SNP were inhibited with N-[2-(p-bromociannamylamino)-ethyl]-5-isoquinolinesulfonamide-dich loride (H89, 10 microM), suggesting the involvement of cyclic AMP dependent protein kinase (PKA). 6. These results suggest that K(ATP) channels play a central role in lymphatic smooth muscle hyperpolarization evoked by a NO-induced increase in cyclic GMP synthesis, as well as by beta-adrenoceptor-mediated production of cyclic AMP. Interestingly, both pathways lead to K(ATP) channels opening through the activation of PKA.
Department of Zoology and Animal Biology, University of Geneva, Switzerland.
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von der Weid
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000378:metabolism; D006168:Guinea Pigs; D007545:Isoproterenol / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D008638:Mesenteric Arteries; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000378:metabolism*; D047428:Protein Kinase Inhibitors; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D013449:Sulfonamides
D000318:Adrenergic beta-Agonists; D004791:Enzyme Inhibitors; D007546:Isoquinolines; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D047428:Protein Kinase Inhibitors; D011943:Receptors, Adrenergic, beta; D013449:Sulfonamides; D005576:Colforsin; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D007545:Isoproterenol; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D005905:Glyburide