title: Adenosine inhibits voltage-dependent Ca2+ influx in cone photoreceptor terminals of the tiger salamander retina.
abstract: Endogenous adenosine has already been shown to inhibit transmitter release from the rod synapse by suppressing Ca(2+) influx through voltage-gated Ca(2+) channels. However, it is not clear how adenosine modulates the cone synapse. Cone photoreceptors, like rod photoreceptors, also possess L-type Ca(2+) channels that regulate the release of L-glutamate. To assess the impact of adenosine on Ca(2+) influx though voltage-gated Ca(2+) channels in cone terminals, whole-cell perforated-patch clamp recording and Ca(2+) imaging with fluo-4 were used on isolated cones and salamander retinal slices. Synaptic markers (VAMP and piccolo) and activity-dependent dye labeling revealed that tiger salamander cone terminals contain a broad, vesicle-filled cytoplasmic extension at the base of the somatic compartment, which is unlike rod terminals that contain one or more thin axons, each terminating in a large bulbous synaptic terminal. The spatiotemporal Ca(2+) responses of the cone terminals do not differ significantly from the Ca(2+) responses of the soma or inner segment like that observed in rods. Whole-cell recording of cone I(Ca) and Ca(2+) imaging of synaptic terminals in cones demonstrate that adenosine inhibited both I(Ca) and the depolarization-evoked Ca(2+) increase in cone terminals in a dose-dependent manner from 1 to 50 muM. These results indicate that, as in rods, adenosine's ability to suppress voltage-dependent Ca(2+) channels at the cone synapse will limit the amount of L-glutamate released. Therefore, adenosine has an inhibitory effect on L-glutamate release at the first synapse, which likely favors elevated adenosine levels in the dark or during dark-adapted conditions.
authors.affiliation: Department of Neurobiology, David Geffen School of Medicine, University of California, Los Angeles, California, USA. sstella@mednet.ucla.edu
authors.forename: Salvatore L
authors.initials: SL
authors.lastname: Stella
authors.forename: Wanda D
authors.initials: WD
authors.lastname: Hu
authors.forename: Alejandro
authors.initials: A
authors.lastname: Vila
authors.forename: Nicholas C
authors.initials: NC
authors.lastname: Brecha
mesh_terms: D000241:Adenosine / Q000378:metabolism* / Q000494:pharmacology; D000557:Ambystoma; D000818:Animals; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D003623:Dark Adaptation / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005456:Fluorescent Dyes; D018698:Glutamic Acid / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009479:Neuropeptides / Q000378:metabolism; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D017949:Retinal Cone Photoreceptor Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013572:Synaptic Vesicles / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D050987:Vesicle-Associated Membrane Protein 1 / Q000378:metabolism; D014785:Vision, Ocular / Q000502:physiology
chemical_list: D015415:Biomarkers; D015220:Calcium Channels; D003598:Cytoskeletal Proteins; D005456:Fluorescent Dyes; D009479:Neuropeptides; C498630:PCLO protein, human; D050987:Vesicle-Associated Membrane Protein 1; D018698:Glutamic Acid; D000241:Adenosine