ATP-sensitive K+ channels in smooth muscle cells of guinea-pig mesenteric lymphatics: role in nitric oxide and beta-adrenoceptor agonist-induced hyperpolarizations

Br J Pharmacol. 1998 Sep;125(1):17-22. doi: 10.1038/sj.bjp.0702026.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism*
  • Adrenergic beta-Agonists / pharmacology*
  • Animals
  • Colforsin / pharmacology
  • Cyclic GMP / metabolism
  • Enzyme Inhibitors / pharmacology
  • Glyburide / pharmacology
  • Guanylate Cyclase / metabolism
  • Guinea Pigs
  • Isoproterenol / pharmacology
  • Isoquinolines / pharmacology
  • Membrane Potentials / drug effects
  • Mesenteric Arteries
  • Muscle, Smooth, Vascular / metabolism*
  • Nitric Oxide / metabolism*
  • Potassium Channel Blockers
  • Potassium Channels / metabolism*
  • Protein Kinase Inhibitors
  • Receptors, Adrenergic, beta / metabolism*
  • Sulfonamides*

Substances

  • Adrenergic beta-Agonists
  • Enzyme Inhibitors
  • Isoquinolines
  • Potassium Channel Blockers
  • Potassium Channels
  • Protein Kinase Inhibitors
  • Receptors, Adrenergic, beta
  • Sulfonamides
  • Colforsin
  • Nitric Oxide
  • Adenosine Triphosphate
  • Guanylate Cyclase
  • Cyclic GMP
  • Isoproterenol
  • N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide
  • Glyburide