title: Calcium-induced calcium release contributes to synaptic release from mouse rod photoreceptors.
abstract: We tested whether calcium-induced calcium release (CICR) contributes to synaptic release from rods in mammalian retina. Electron micrographs and immunofluorescent double labeling for the sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA2) and synaptic ribbon protein, ribeye, showed a close association between ER and synaptic ribbons in mouse rod terminals. Stimulating CICR with 10 microM ryanodine evoked Ca(2+) increases in rod terminals from mouse retinal slices visualized using confocal microscopy with the Ca(2+)-sensitive dye, Fluo-4. Ryanodine also stimulated membrane depolarization of individual mouse rods. Inhibiting CICR with a high concentration of ryanodine (100 microM) reduced the electroretinogram (ERG) b-wave but not a-wave consistent with inhibition of synaptic transmission from rods. Ryanodine (100 microM) also inhibited light-evoked voltage responses of individual rod bipolar cells (RBCs) and presumptive horizontal cells recorded with perforated patch recording techniques. A presynaptic site of action for ryanodine's effects is further indicated by the finding that ryanodine (100 microM) did not alter currents evoked in voltage-clamped RBCs by puffing the mGluR6 antagonist, (RS)-alpha-cyclopropyl-4-phosphonophenylglycine (CPPG), onto bipolar cell dendrites in the presence of the mGluR6 agonist L-(+)-2-amino-4-phosphonobutyric acid (L-AP4). Ryanodine (100 microM) also inhibited glutamatergic outward currents in RBCs evoked by electrical stimulation of rods using electrodes placed in the outer segment layer. Together, these results indicate that, like amphibian retina, CICR contributes to synaptic release from mammalian (mouse) rods. By boosting synaptic release in darkness, CICR may improve the detection of small luminance changes by post-synaptic neurons.
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, NE 68198, USA.
authors.forename: N
authors.initials: N
authors.lastname: Babai
authors.forename: C W
authors.initials: CW
authors.lastname: Morgans
authors.forename: W B
authors.initials: WB
authors.lastname: Thoreson
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003712:Dendrites / Q000187:drug effects / Q000502:physiology; D005071:Evoked Potentials / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D010775:Photic Stimulation; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D012160:Retina / Q000187:drug effects / Q000502:physiology; D051245:Retinal Bipolar Cells / Q000187:drug effects / Q000502:physiology; D051248:Retinal Horizontal Cells / Q000187:drug effects / Q000502:physiology; D017948:Retinal Rod Photoreceptor Cells / Q000187:drug effects / Q000502:physiology*; D012433:Ryanodine / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D014785:Vision, Ocular / Q000187:drug effects / Q000502:physiology
chemical_list: D018094:Receptors, Metabotropic Glutamate; C113897:metabotropic glutamate receptor 6; D012433:Ryanodine; D018698:Glutamic Acid; D002118:Calcium