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

摘要: 1 Intracellular microelectrode recordings were performed to investigate the membrane K+ conductances involved in smooth muscle hyperpolarization of lymphatic vessels guinea-pig mesentery. 2 Nitric oxide (NO), released either by endothelium after acetylcholine (ACh; 10 μM) stimulation or sodium nitroprusside (SNP; 50–100 μM), hyperpolarized muscle. These responses inhibited with guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazole [4,3-a]quinoxalin-1-one (ODQ, 10 μM). 3 ACh and SNP-induced hyperpolarizations (by about 90%) upon application ATP-sensitive K+(KATP) channel blocker, glibenclamide (10 μM), 4-aminopyridine (2.5 mM), but not affected Ca2+-activated channels penitrem A (100 nM). 4 Hyperpolarization caused opener, cromakalim (0.1–10 μM), isoprenaline (0.1 μM) forskolin (0.5 μM) all significantly blocked glibenclamide. 5 Hyperpolarization evoked ACh SNP N-[2-(p-bromociannamylamino)-ethyl]-5-isoquinolinesulfonamide-dichloride (H89, 10 μM), suggesting involvement cyclic AMP dependent protein kinase (PKA). 6 These results suggest that KATP play a central role NO-induced increase GMP synthesis, as well β-adrenoceptor-mediated production AMP. Interestingly, both pathways lead opening through activation PKA. British Journal Pharmacology (1998) 125, 17–22; doi:10.1038/sj.bjp.0702026