D2 DOPAMINE RECEPTOR-MEDIATED INHIBITION OF A HYPERPOLARIZATION-ACTIVATED CURRENT IN ROD PHOTORECEPTORS. Akopian, Abram and Paul Witkovsky. Dept. Ophthalmology and Dept. Physiology & Neuroscience, New York University Medical Center, 550 First Avenue, New York, N.Y. 10016.
APStracts 3:0088N, 1996.
1. Using the whole-cell patch clamp method we investigated the effect of dopamine on a hyperpolarization-activated current (I h ) in the inner segments of rod photoreceptors of the Xenopus retina. 2. I h was elicited by hyperpolarizing voltage steps to -120 mV from a holding potential of -40 mV. Dopamine reversibly reduced I h in a dose-dependent manner. Dopamine-mediated inhibition of I h was blocked by the D2 dopamine antagonist sulpiride. 3. The D2 dopamine agonist quinpirole (0.1-20 [mu] M) inhibited I h whereas the D1 agonist SKF-38393 (100 [mu] M) had no effect on I h . Quinpirole-induced inhibition of I h was blocked by sulpiride, but not by the D4 antagonist, clozapine. The D3 agonists 7-OH-DPAT and trans -7-OH-PIPAT- maleate were, respectively, 5 and 100 x less effective than quinpirole in inhibiting I h . 4. Quinpirole failed to reduce I h when the internal solution contained GDP [beta] S (500 [mu] M). Internal application of GTP [gamma] S (300 [mu] M) progressively and irreversibly reduced I h and blocked a further reduction by quinpirole, indicating that the inhibition of I h by quinpirole involves a G- protein. 5. The inhibition of I h by quinpirole was not affected by intracellularly applied 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. I h was not altered when the patch pipette contained a nominally Ca 2+ -free internal solution, but the inhibition of I h by quinpirole was abolished, suggesting an involvement of Ca 2+ in the quinpirole-induced effect. 7. We conclude that a D2 dopamine receptor modulates I h through the activation of a G-protein and that intracellular Ca 2+ , but not cAMP, plays a key role in this process. 8. The reduction of I h by dopamine may reduce the ability of rods to signal time- modulated light stimuli.

Received 18 January 1996; accepted in final form 1 May 1996.
APS Manuscript Number J28-6.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 19 May 96