D2 dopamine receptor-mediated inhibition of a hyperpolarization-activated current in rod photoreceptors

J Neurophysiol. 1996 Sep;76(3):1828-35. doi: 10.1152/jn.1996.76.3.1828.

Abstract

1. Using the whole cell patch clamp method, we investigated the effect of dopamine on a hyperpolarization-activated current (Ih) in the inner segments of rod photoreceptors of the Xenopus retina. 2. Ih was elicited by hyperpolarizing voltage steps to -120 mV from a holding potential of -40 mV. Dopamine reversibly reduced Ih in a dose-dependent manner. Dopamine-mediated inhibition of Ih was blocked by the D2 dopamine antagonist sulpiride. 3. The D2 dopamine agonist quinpirole (0.1-20 microM) inhibited Ih whereas the D1 agonist SKF-38393 (100 microM) had no effect on Ih. Quinpirole-induced inhibition of Ih was blocked by sulpiride, but not by the D4 antagonist, clozapine. The D3 agonists (+/-)-7-hydroxy-2-dipropylaminotetralin hydrochloride and trans-7-hydroxy-2[N-propyl-N-(3'-iodo-2'-propenyl)amino]-tetralin maleate were, respectively, 5 and 100 times less effective than quinpirole in inhibiting Ih. 4. Quinpirole failed to reduce Ih when the internal solution contained GDP beta S (500 microM). Internal application GTP gamma S (300 microM) progressively and irreversibly reduced Ih and blocked a further reduction by quinpirole, indicating that the inhibition of Ih by quinpirole involves a G protein. 5. The inhibition of Ih by quinpirole was not affected by intracellularly applied adenosine 3',5'-cyclic monophosphate (cAMP) or by the protein kinase inhibitor H-7, indicating that a cAMP-mediated second messenger cascade does not participate in the dopamine-mediated inhibition. 6. Ih was not altered when the patch pipette contained a nominally Ca(2+)-free internal solution, but the inhibition of Ih by quinpirole was abolished, suggesting an involvement of Ca(2+) in the quinpirole-induced effect. 7. We conclude that a D2 dopamine receptor modulates Ih through the activation of a G protein and that intracellular Ca2+, but not cAMP, plays a key role in this process. 8. The reduction of Ih by dopamine may reduce the ability of rods to signal time-modulated light stimuli.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / pharmacology
  • Animals
  • Cyclic AMP / physiology
  • Dopamine / physiology
  • Dopamine Agonists / pharmacology
  • Dopamine D2 Receptor Antagonists
  • Electrophysiology
  • Enzyme Inhibitors / pharmacology
  • GTP-Binding Proteins / metabolism
  • In Vitro Techniques
  • Male
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Patch-Clamp Techniques
  • Photoreceptor Cells / drug effects
  • Photoreceptor Cells / physiology*
  • Quinpirole / pharmacology
  • Receptors, Dopamine D2 / agonists
  • Receptors, Dopamine D2 / physiology*
  • Retinal Rod Photoreceptor Cells / drug effects
  • Retinal Rod Photoreceptor Cells / physiology*
  • Xenopus

Substances

  • Dopamine Agonists
  • Dopamine D2 Receptor Antagonists
  • Enzyme Inhibitors
  • Receptors, Dopamine D2
  • Quinpirole
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • Cyclic AMP
  • GTP-Binding Proteins
  • Dopamine