Dopamine D1 receptor modulation of calcium channel currents in horizontal cells of mouse retina.
J Neurophysiol
; 116(2): 686-97, 2016 08 01.
Article
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| MEDLINE
| ID: mdl-27193322
ABSTRACT
Horizontal cells form the first laterally interacting network of inhibitory interneurons in the retina. Dopamine released onto horizontal cells under photic and circadian control modulates horizontal cell function. Using isolated, identified horizontal cells from a connexin-57-iCre × ROSA26-tdTomato transgenic mouse line, we investigated dopaminergic modulation of calcium channel currents (ICa) with whole cell patch-clamp techniques. Dopamine (10 µM) blocked 27% of steady-state ICa, an action blunted to 9% in the presence of the L-type Ca channel blocker verapamil (50 µM). The dopamine type 1 receptor (D1R) agonist SKF38393 (20 µM) inhibited ICa by 24%. The D1R antagonist SCH23390 (20 µM) reduced dopamine and SKF38393 inhibition. Dopamine slowed ICa activation, blocking ICa by 38% early in a voltage step. Enhanced early inhibition of ICa was eliminated by applying voltage prepulses to +120 mV for 100 ms, increasing ICa by 31% and 11% for early and steady-state currents, respectively. Voltage-dependent facilitation of ICa and block of dopamine inhibition after preincubation with a Gßγ-blocking peptide suggested involvement of Gßγ proteins in the D1R-mediated modulation. When the G protein activator guanosine 5'-O-(3-thiotriphosphate) (GTPγS) was added intracellularly, ICa was smaller and showed the same slowed kinetics seen during D1R activation. With GTPγS in the pipette, additional block of ICa by dopamine was only 6%. Strong depolarizing voltage prepulses restored the GTPγS-reduced early ICa amplitude by 36% and steady-state ICa amplitude by 3%. These results suggest that dopaminergic inhibition of ICa via D1Rs is primarily mediated through the action of Gßγ proteins in horizontal cells.
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Base de datos:
MEDLINE
Asunto principal:
Canales de Calcio
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Receptores de Dopamina D1
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Células Horizontales de la Retina
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Potenciales de la Membrana
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
J Neurophysiol
Año:
2016
Tipo del documento:
Article