title: Nitric oxide donors inhibit spontaneous depolarizations by L-type Ca2+ currents in alveolar epithelial cells.
abstract: L2 cells, a cloned pneumocyte-derived cell line, express voltage-dependent L-type Ca2+ channels, causing transient depolarizing spikes of the membrane potential (Vm) [P. Dietl, T. Haller, B. Wirleitner, H. Völkl, F. Friedrich, and J. Striessing. Am. J. Physiol. 269 (Lung Cell. Mol. Physiol. 13): L873-L883, 1995]. In this study, we examined the effect of nitric oxide (NO)- and guanosine 3',5'-cyclic monophosphate (cGMP)-dependent cell signaling on the activity of L-type Ca2+ channels. Using conventional microelectrodes, spontaneous depolarizations (SD) of Vm by activation of these channels are regularly seen in the presence of 10 mM bath Sr2+. The NO donors sodium nitroprusside (SNP; 1 mM), 3-morpholinosydnonimine (SIN-1; 100 microM), as well as S-nitroso-N-acetyl-D,L-penicillamine (SNAP; 10 microM) caused a significant reduction of the frequency of Sr(2+)-induced SD. These effects were completely reversed by 6-anilino-5,8-quinolinequinone (10 microM), an inhibitor of the soluble guanylyl cyclase, and could be mimicked by 8-bromoguanosine 3'5'-cyclic monophosphate (8-BrcGMP; 100 microM). Perforated patch-clamp experiments revealed that 8-BrcGMP exerted a significant decrease of the depolarization-induced L-type Sr2+ current in the majority of tested cells. Consistent with the dependency of these NO-mediated effects on cGMP, incubation of L2 cells with SNP, SIN-1, and SNAP lead to a pronounced increase of cellular cGMP concentration. We conclude that the NO donors inhibit the activity of L-type Ca2+ channels in L2 cells via a cGMP-dependent pathway. In the alveoli, this might occur under conditions associated with the release of NO.
authors.affiliation: Division for General and Surgical Intensive Care Medicine, University of Innsbruck, Austria.
authors.forename: W
authors.initials: W
authors.lastname: Schobersberger
authors.forename: F
authors.initials: F
authors.lastname: Friedrich
authors.forename: G
authors.initials: G
authors.lastname: Hoffmann
authors.forename: H
authors.initials: H
authors.lastname: Völkl
authors.forename: P
authors.initials: P
authors.lastname: Dietl
mesh_terms: D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D020746:Calcium Channels, L-Type; D002460:Cell Line; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004848:Epithelium / Q000187:drug effects / Q000502:physiology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D008839:Microelectrodes; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology*; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000502:physiology*; D051381:Rats; D026423:S-Nitroso-N-Acetylpenicillamine; D015398:Signal Transduction; D013324:Strontium / Q000494:pharmacology; D013997:Time Factors
chemical_list: D000634:Aminoquinolines; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D004791:Enzyme Inhibitors; D009599:Nitroprusside; C016276:8-bromocyclic GMP; C002385:linsidomine; D026423:S-Nitroso-N-Acetylpenicillamine; C041715:6-anilino-5,8-quinolinedione; D008981:Molsidomine; D006162:Guanylate Cyclase; D010396:Penicillamine; D006152:Cyclic GMP; D013324:Strontium