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

Sep 1, 1996Journal of neurophysiology

How D2 dopamine receptors reduce a specific electrical current in rod eye cells

AI simplified

Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

Dopamine reduced the hyperpolarization-activated current (Ih) in rod photoreceptors, with an effect that is dose-dependent and reversible.

Inhibition of Ih by dopamine was blocked by the D2 dopamine antagonist sulpiride.
The D2 receptor agonist quinpirole inhibited Ih, while the D1 agonist SKF-38393 had no effect.
Quinpirole's inhibitory effect on Ih involved a G protein, as indicated by the failure of quinpirole to reduce Ih in the presence of GDP beta S.
Internal application of GTP gamma S reduced Ih and prevented further inhibition by quinpirole.
The inhibition of Ih by quinpirole was not affected by cAMP or a protein kinase inhibitor, suggesting a non-cAMP mediated pathway.
Ih remained unchanged in the absence of Ca2+, but quinpirole's inhibition of Ih was lost, indicating a role for Ca2+ in this process.

AI simplified

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.

Full Text

Full text is available at the source.

View full text ↗

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

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief