Caffeine-sensitive calcium stores regulate synaptic transmission from retinal rod photoreceptors.
We investigated the role of caffeine-sensitive intracellular stores in regulating intracellular calcium ([Ca(2+)](i)) and glutamatergic synaptic transmission from rod photoreceptors. Caffeine transiently elevated and then markedly depressed [Ca(2+)](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 [Ca(2+)](i), on glutamate release, and on I(Ca) in rods can be attributed to calcium release from stores: (1) caffeine's actions on [Ca(2+)](i) and I(Ca) were reduced by intracellular BAPTA and barium substitution for calcium, (2) other nonxanthine store-releasing compounds, such as thymol and chlorocresol, also depressed [Ca(2+)](i), and (3) the magnitude of [Ca(2+)](i) depression depended on basal [Ca(2+)](i) before caffeine. We propose that caffeine-released calcium reduces I(Ca) in rods by an as yet unidentified intracellular signaling mechanism. To account for the depression of [Ca(2+)](i) below rest levels and the increased fall rate of [Ca(2+)](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 [Ca(2+)](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.
Krizaj
D
D
Departments of Ophthalmology and Physiology, University of California at San Francisco School of Medicine, San Francisco, California 94143-0730, USA.
Bao
J X
JX
Schmitz
Y
Y
Witkovsky
P
P
Copenhagen
D R
DR
D000557:Ambystoma; D000818:Animals; D001464:Barium / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology*; D015220:Calcium Channels / Q000502:physiology; D002614:Chelating Agents / Q000494:pharmacology; D003408:Cresols / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004594:Electrophysiology; D066298:In Vitro Techniques; D007700:Kinetics; D008959:Models, Neurological; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology*; D017948:Retinal Rod Photoreceptor Cells / Q000187:drug effects / Q000502:physiology*; D012433:Ryanodine / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013943:Thymol / Q000494:pharmacology; D014982:Xenopus laevis
D015220:Calcium Channels; D002614:Chelating Agents; D003408:Cresols; D012433:Ryanodine; D001464:Barium; C006984:chlorocresol; D002110:Caffeine; D013943:Thymol; D004533:Egtazic Acid; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium