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Dopamine released onto horizontal cells under photic and circadian control modulates horizontal cell function. Using isolated, identified horizontal cells from a connexin-57-iCre \u00d7 ROSA26-tdTomato transgenic mouse line, we investigated dopaminergic modulation of calcium channel currents ( I<jats:sub>Ca<\/jats:sub>) with whole cell patch-clamp techniques. Dopamine (10 \u03bcM) blocked 27% of steady-state I<jats:sub>Ca<\/jats:sub>, an action blunted to 9% in the presence of the L-type Ca channel blocker verapamil (50 \u03bcM). The dopamine type 1 receptor (D1R) agonist SKF38393 (20 \u03bcM) inhibited I<jats:sub>Ca<\/jats:sub>by 24%. The D1R antagonist SCH23390 (20 \u03bcM) reduced dopamine and SKF38393 inhibition. Dopamine slowed I<jats:sub>Ca<\/jats:sub>activation, blocking I<jats:sub>Ca<\/jats:sub>by 38% early in a voltage step. Enhanced early inhibition of I<jats:sub>Ca<\/jats:sub>was eliminated by applying voltage prepulses to +120 mV for 100 ms, increasing I<jats:sub>Ca<\/jats:sub>by 31% and 11% for early and steady-state currents, respectively. Voltage-dependent facilitation of I<jats:sub>Ca<\/jats:sub>and block of dopamine inhibition after preincubation with a G\u03b2\u03b3-blocking peptide suggested involvement of G\u03b2\u03b3 proteins in the D1R-mediated modulation. When the G protein activator guanosine 5\u2032- O-(3-thiotriphosphate) (GTP\u03b3S) was added intracellularly, I<jats:sub>Ca<\/jats:sub>was smaller and showed the same slowed kinetics seen during D1R activation. With GTP\u03b3S in the pipette, additional block of I<jats:sub>Ca<\/jats:sub>by dopamine was only 6%. Strong depolarizing voltage prepulses restored the GTP\u03b3S-reduced early I<jats:sub>Ca<\/jats:sub>amplitude by 36% and steady-state I<jats:sub>Ca<\/jats:sub>amplitude by 3%. These results suggest that dopaminergic inhibition of I<jats:sub>Ca<\/jats:sub>via D1Rs is primarily mediated through the action of G\u03b2\u03b3 proteins in horizontal cells.<\/jats:p>","DOI":"10.1152\/jn.00990.2015","type":"journal-article","created":{"date-parts":[[2016,5,19]],"date-time":"2016-05-19T08:34:18Z","timestamp":1463646858000},"page":"686-697","source":"Crossref","is-referenced-by-count":25,"title":["Dopamine D1 receptor modulation of calcium channel currents in horizontal cells of mouse retina"],"prefix":"10.1152","volume":"116","author":[{"given":"Xue","family":"Liu","sequence":"first","affiliation":[{"name":"Biomaterials and Live Cell Imaging Institute, Chongqing University of Science and Technology, Chongqing, People's Republic of China;"},{"name":"Department of Neurobiology and Jules Stein Eye Institute, David Geffen School of Medicine, University of California, Los Angeles, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James C. 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