Purchase this article with an account.
N Zhang, E Townes-Anderson; Activation of the Nitric Oxide-cGMP Signaling System Stimulates Presynaptic Plasticity in Salamander Cone Cells In Vitro . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2702.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Purpose: We have established that cone cells differ from rod cells in that they require cGMP-gated channels instead of L-type Ca2+ channels for synaptic development (Zhang & Townes-Anderson, IOVS 42:S365, 2001). In the present study, we investigated the effects of the nitric oxide (NO)-cGMP signaling system on the formation of presynaptic terminals by cultured cone cells. Methods: Isolated photoreceptors from adult tiger salamanders were incubated for 3 days in a Ca2+-containing medium with the following reagents added separately or in combination: an NO donor, (+)-S-nitroso-N-acetylpenicillamine (SNAP); a specific inhibitor of soluble guanylyl cyclase, 1H-[1,2,4]oxadiazolo-[4,2-a]quinoxalin-1-one (ODQ); a specific activator of soluble guanylyl cyclase, 3-(5-hydroxymethy-2-furyl)-1-benzylindazole (YC-1); and a cGMP analogue, 8Br-cGMP. The growth of neuritic processes and the formation of presynaptic varicosities were examined in cones identified by immunostaining and morphology. Control cultures received no reagents. Results: NO is a potent activator of soluble guanylyl cyclase (sGC). The NO donor SNAP (1mM) caused an increase in the length of the longest process (17.4%, p<0.05) and the number of presynaptic varicosities (80.7%, p<0.001). Both YC-1 (1µM), an activator of sGC, and 8Br-cGMP (350mM) also caused a significant increase in varicosities (42.9% and 80.0% respectively, p<0.001). Furthermore, the growth of the neuritic structures was reduced by an inhibitor of sGC, ODQ (50µM, p<0.001), either in the presence or absence of SNAP. However, if the application of ODQ was delayed for 24hr, it no longer inhibited the growth of the neuritic structures. Conclusion: In cone cells, presynaptic development is stimulated by activation of the NO-sGS-cGMP signaling system in which the activity of sGC is required specifically during the first day in culture but not at later stages.
This PDF is available to Subscribers Only