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

Activation of D₂-like dopamine receptors in rods with quinpirole stimulates L-type calcium currents (I_Ca). 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 I_Ca, we tested the hypothesis that enhancement of I_Ca, with the D₂/D₄ receptor agonist, quinpirole, increases calcium-activated chloride currents (I_Cl(Ca)) causing an efflux of Cl^- from rods that would provide a negative feedback inhibition of I_Ca. 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⁺], measured with Fura-2 in rods, a finding consistent with inhibition of synaptic transmission from rods. Electrophysiological and Cl^--imaging experiments indicated E_Cl in rods is ∼ -20 mV. Quinpirole enhanced I_Cl(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 I_Cl(Ca) was inhibited with niflumic acid, quinpirole enhanced both I_Ca 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 I_Ca by quinpirole is followed by a stimulation of Cl^- currents, including I_Cl(Ca). The net result is a Cl^- efflux that inhibits depolarization-evoked increases in [Ca²⁺]_i and synaptic transmission from rods.