title: D2-like dopamine receptors promote interactions between calcium and chloride channels that diminish rod synaptic transfer in the salamander retina.
abstract: Activation of D2-like dopamine receptors in rods with quinpirole stimulates L-type calcium currents (ICa). This result appears inconsistent with studies showing that D2-like dopamine receptor activation diminishes rod signals in second-order retinal neurons. Since small reductions in [Cl-] can inhibit photoreceptor ICa, we tested the hypothesis that enhancement of ICa with the D2/D4 receptor agonist, quinpirole, increases calcium-activated chloride currents (ICl(Ca)) causing an efflux of Cl- from rods that would provide a negative feedback inhibition of ICa. In agreement with studies from Xenopus, quinpirole reduced rod input to second-order neurons of tiger salamander retina without significantly altering rod voltage responses. Quinpirole also diminished the amplitude of depolarization-evoked increases in [Ca2+]i measured with Fura-2 in rods, a finding consistent with inhibition of synaptic transmission from rods. Electrophysiological and Cl(-)-imaging experiments indicated ECl in rods is approximately -20 mV. Quinpirole enhanced ICl(Ca) and elicited an efflux of Cl- at the resting potential. A similar Cl- efflux was produced by extracellular replacement of 24 mM Cl- with CH3SO4- and this low Cl- solution inhibited Ca2+ responses to a similar degree as quinpirole did. When ICl(Ca) was inhibited with niflumic acid, quinpirole enhanced both ICa and depolarization-evoked increases in [Ca2+]i. Furthermore, with niflumic acid, quinpirole no longer inhibited rod inputs into horizontal and bipolar cells. These results suggest an initial enhancement of ICa by quinpirole is followed by a stimulation of Cl- currents, including ICl(Ca). The net result is a Cl- efflux that inhibits depolarization-evoked increases in [Ca2+]i and synaptic transmission from rods.
authors.affiliation: Department of Ophthalmology, University of Nebraska Medical Center, Omaha 68198-5540, USA. wbthores@unmc.edu
authors.forename: Wallace B
authors.initials: WB
authors.lastname: Thoreson
authors.forename: Salvatore L
authors.initials: SL
authors.lastname: Stella
authors.forename: Eric I
authors.initials: EI
authors.lastname: Bryson
authors.forename: John
authors.initials: J
authors.lastname: Clements
authors.forename: Paul
authors.initials: P
authors.lastname: Witkovsky
mesh_terms: D000557:Ambystoma; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000502:physiology*; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology*; D002712:Chlorides / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology; D004594:Electrophysiology; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000378:metabolism; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D009544:Niflumic Acid / Q000494:pharmacology; D009994:Osmolar Concentration; D019257:Quinpirole / Q000494:pharmacology; D017448:Receptors, Dopamine D2 / Q000502:physiology*; D012160:Retina / Q000502:physiology*; D017948:Retinal Rod Photoreceptor Cells / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
chemical_list: D020746:Calcium Channels, L-Type; D018118:Chloride Channels; D002712:Chlorides; D018491:Dopamine Agonists; D017448:Receptors, Dopamine D2; D019257:Quinpirole; D009544:Niflumic Acid; D002118:Calcium