Beta-adrenoceptor-mediated hyperpolarization in lymphatic smooth muscle of guinea pig mesentery.
Intracellular microelectrode recordings were performed to investigate the consequences of beta-adrenoceptor activation in smooth muscle of guinea pig mesenteric lymphatic vessels. Isoproterenol (Iso) hyperpolarized the membrane with an associated increase in membrane conductance and decreased the amplitude of spontaneous transient depolarizations. Iso effects were mimicked by forskolin (FSK), 3-isobutyl-1-methylxanthine, and two adenosine 3',5'-cyclic monophosphate (cAMP) derivatives. Iso- and FSK-induced hyperpolarizations were inhibited by H89, an inhibitor of cAMP-dependent protein kinase A, increased in K+-free solution, but were not affected by ouabain or by the nitric oxide synthase inhibitor N(omega)-nitro-L-arginine. They were partially inhibited by 20 mM tetraethylammonium (approximately 40%) or by 2.5 mM 4-aminopyridine (approximately 55%). The-Iso-induced hyperpolarization was partially inhibited by iberiotoxin (20 nM) and charybdotoxin (40 nM), whereas the FSK-induced hyperpolarization was less affected. In cells where the Iso-induced hyperpolarization was decreased by 40 microM 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, acetoxymethyl ester form, the FSK-induced hyperpolarization was little changed. Our results indicate that in guinea pig mesenteric lymphatic vessels, beta-adrenoceptor stimulation activates a protein kinase A-dependent K+ conductance, involving more than one channel type.
Von der Weid
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Neuroscience Group, Discipline of Human Physiology, Faculty of Medicine and Health Sciences, University of Newcastle, Callahan NSW, Australia.
Van Helden
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D000818:Animals; D002118:Calcium; D002614:Chelating Agents / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004594:Electrophysiology; D005260:Female; D006168:Guinea Pigs; D007546:Isoquinolines / Q000494:pharmacology; D008208:Lymphatic System / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008643:Mesentery / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D013449:Sulfonamides
D002614:Chelating Agents; D007546:Isoquinolines; D011943:Receptors, Adrenergic, beta; D013449:Sulfonamides; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D004533:Egtazic Acid; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D002118:Calcium