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D2-like dopamine receptors promote interactions between calcium and chloride channels that diminish rod synaptic transfer in the salamander retina

Published online by Cambridge University Press:  05 September 2002

WALLACE B. THORESON
Affiliation:
Department of Ophthalmology, University of Nebraska Medical Center, Omaha Department of Pharmacology, University of Nebraska Medical Center, Omaha
SALVATORE L. STELLA
Affiliation:
Department of Ophthalmology, University of Nebraska Medical Center, Omaha Department of Pharmacology, University of Nebraska Medical Center, Omaha
ERIC J. BRYSON
Affiliation:
Department of Ophthalmology, University of Nebraska Medical Center, Omaha
JOHN CLEMENTS
Affiliation:
Department of Ophthalmology, University of Nebraska Medical Center, Omaha
PAUL WITKOVSKY
Affiliation:
Departments of Ophthalmology and Physiology and Neuroscience, New York University Medical Center, New York City

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]i 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 ∼ −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.

Type
Research Article
Copyright
2002 Cambridge University Press

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