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S.L. Stella, W.D. Hu, N.C. Brecha; Adenosine Suppresses Transmitter Release by Inhibiting Calcium Channels in Cone Photoreceptors of the Tiger Salamander Retina . Invest. Ophthalmol. Vis. Sci. 2005;46(13):4534.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose:ATP and adenosine are released from the retina and endogenous adenosine has been shown to inhibit excitatory transmission in the outer retina. It has been proposed that adenosine release occurs in the dark, when photoreceptors are depolarized and L–glutamate release from photoreceptors is at its greatest. The tonic release of L–glutamate is regulated by the activity of L–type calcium channels present on photoreceptors. L–type Ca2+ channels regulate the release of L–glutamate from cone photoreceptors. Activation of adenosine receptors in the CNS has been shown to inhibit transmitter release through inhibition of voltage–dependent Ca2+ influx through Ca2+ channels in rod photoreceptors. We therefore tested whether adenosine could inhibit Ca2+ influx through L–type Ca2+ channels and alter exocytosis from isolated cone photoreceptors. Methods:[Ca2+]i changes in cones were assessed using the dye, fluo–4, and exocytosis was monitored with the activity dependent dye, Synaptored–C2. Immunocytochemistry was performed on isolated cones and retinal sections, to determine the localization of adenosine receptors (A1, A2A, A2B, A3). Results:Adenosine inhibited the K+–evoked Ca2+ increases in cones in a concentration–dependent manner (1–50 µM). K+–evoked depolarizations in cones resulted in destaining of Synaptored–C2 in cone terminals, which was inhibited by adenosine. A2 receptor immunoreactivity was localized to photoreceptors. The pharmacological subtype of adenosine receptor mediating the inhibition of voltage–dependent calcium channels was investigated using selective adenosine receptor agonists [A1 (N6–Cyclopentyladenosine), A2A (CGS 21680), A3 (HEMADO)]. Conclusions:These results suggest that adenosine inhibits exocytosis from cones by inhibiting voltage–dependent Ca2+ channels. Therefore, adenosine regulates cone transmitter release in the outer retina by suppressing L–type Ca2+ channels.
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