AJP - Lung Cellular and Molecular Physiology, Vol 272, Issue 6 1092-L1097, Copyright © 1997 by American Physiological Society

ARTICLES

Nitric oxide donors inhibit spontaneous depolarizations by L-type Ca2+ currents in alveolar epithelial cells

W. Schobersberger, F. Friedrich, G. Hoffmann, H. Volkl and P. Dietl
Division for General and Surgical Intensive Care Medicine, University of Innsbruck, Austria.

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. Volkl, 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.

This article has been cited by other articles:

				C.-W. Sun, M. Alonso-Galicia, M. R. Taheri, J. R. Falck, D. R. Harder, and R. J. Roman Nitric Oxide-20–Hydroxyeicosatetraenoic Acid Interaction in the Regulation of K+ Channel Activity and Vascular Tone in Renal Arterioles Circ. Res., November 30, 1998; 83(11): 1069 - 1079. [Abstract] [Full Text] [PDF]

				T. Haller, J. Ortmayr, F. Friedrich, H. Volkl, and P. Dietl Dynamics of surfactant release in alveolar type II cells PNAS, February 17, 1998; 95(4): 1579 - 1584. [Abstract] [Full Text] [PDF]