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The Journal of Neuroscience, September 1, 1999, 19(17):7249-7261
Caffeine-Sensitive Calcium Stores Regulate Synaptic Transmission from Retinal Rod Photoreceptors
David Krizaj1, Jian-Xin Bao1, Yvonne Schmitz2, Paul Witkovsky2, 3, and David R. Copenhagen1 1 Departments of Ophthalmology and Physiology, University of California at San Francisco School of Medicine, San Francisco, California 94143-0730, and Departments of 2 Physiology and Neuroscience and 3 Ophthalmology, New York University Medical Center, New York, New York 10016
We investigated the role of caffeine-sensitive intracellular stores in regulating intracellular calcium ([Ca2+]i) and glutamatergic synaptic transmission from rod photoreceptors. Caffeine transiently elevated and then markedly depressed [Ca2+]i to below prestimulus levels in rod inner segments and synaptic terminals. Concomitant with the depression was a reduction of glutamate release and a hyperpolarization of horizontal cells, neurons postsynaptic to rods. Caffeine did not affect the rods' membrane potentials indicating that caffeine likely acted via some mechanism(s) other than a voltage-dependent deactivation of the calcium channels. Most of caffeine's depressive action on [Ca2+]i, on glutamate release, and on ICa in rods can be attributed to calcium release from stores: (1) caffeine's actions on [Ca2+]i and ICa were reduced by intracellular BAPTA and barium substitution for calcium, (2) other nonxanthine store-releasing compounds, such as thymol and chlorocresol, also depressed [Ca2+]i, and (3) the magnitude of [Ca2+]i depression depended on basal [Ca2+]i before caffeine. We propose that caffeine-released calcium reduces ICa in rods by an as yet unidentified intracellular signaling mechanism. To account for the depression of [Ca2+]i below rest levels and the increased fall rate of [Ca2+]i with higher basal calcium, we also propose that caffeine-evoked calcium release from stores activates a calcium transporter that, via sequestration into stores or extrusion, lowers [Ca2+]i and suppresses glutamate release. The effects of store-released calcium reported here operate at physiological calcium concentrations, supporting a role in regulating synaptic signaling in vivo.
Key words: photoreceptor; rod; calcium; caffeine; intracellular calcium stores; glutamate release
Copyright © 1999 Society for Neuroscience 0270-6474/99/19177249-13$05.00/0
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