W. Schobersberger et al., NITRIC-OXIDE DONORS INHIBIT SPONTANEOUS DEPOLARIZATIONS BY L-TYPE CA2-CELLS( CURRENTS IN ALVEOLAR EPITHELIAL), American journal of physiology. Lung cellular and molecular physiology, 16(6), 1997, pp. 1092-1097
L2 cells, a cloned pneumocyte-derived cell line, express voltage-depen
dent L-type Ca2+ channels, causing transient depolarizing spikes of th
e membrane potential (V-m) [P. Dietl, T. Haller, B. Wirleitner, H. Vol
kl, F. Friedrich, and J. Striessnig. Am. J. Physiol. 269 (Lung Cell. M
ot. Physiol. 13): L873-L883, 1995]. In this study, we examined the eff
ect of nitric oxide (NO)- and guanosine 3',5'-cyclic monophosphate (cG
MP)-dependent cell signaling on the activity of L-type Ca2+ channels.
Using conventional microelectrodes, spontaneous depolarizations (SD) o
f V-m by activation of these channels are regularly seen in the presen
ce of 10 mM bath Sr2+. Th, NO donors sodium nitroprusside (SNP; 1 mM),
3-morpholinosydnonimine (SIN-1; 100 mu M), as well as S-nitroso-N-ace
tyl-D,L-penicillamine (SNAP; 10 mu M) caused a significant reduction o
f the frequency of Sr2+-induced SD. These effects were completely reve
rsed by 6-anilino-5,8-quinolinequinone (10 mu M), an inhibitor of the
soluble guanylyl cyclase, and could be mimicked by 8-bromoguanosine 3'
,5'-cyclic monophosphate (8-BrcGMP; 100 mu M). Perforated patch-clamp
experiments revealed that 8-BrcGMP exerted a significant decrease of t
he depolarization-induced L-type Sr2+ current in the majority of teste
d cells. Consistent with the dependency of these NO-mediated effects o
n cGMP, incubation of L2 cells with SNP, SIN-1, and SNAP lead to a pro
nounced 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 cond
itions associated with the release of NO.