title: Dopamine D1 receptor modulation of calcium channel currents in horizontal cells of mouse retina.
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 Gβγ-blocking peptide suggested involvement of Gβγ 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 Gβγ proteins in horizontal cells.
authors.affiliation: Biomaterials and Live Cell Imaging Institute, Chongqing University of Science and Technology, Chongqing, People's Republic of China; Department of Neurobiology and Jules Stein Eye Institute, David Geffen School of Medicine, University of California, Los Angeles, California;
authors.forename: Xue
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Neurobiology and Jules Stein Eye Institute, David Geffen School of Medicine, University of California, Los Angeles, California;
authors.forename: James C R
authors.initials: JC
authors.lastname: Grove
authors.affiliation: Department of Neurobiology and Jules Stein Eye Institute, David Geffen School of Medicine, University of California, Los Angeles, California; Department of Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California; and.
authors.forename: Arlene A
authors.initials: AA
authors.lastname: Hirano
authors.affiliation: Department of Neurobiology and Jules Stein Eye Institute, David Geffen School of Medicine, University of California, Los Angeles, California; Department of Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California; and.
authors.forename: Nicholas C
authors.initials: NC
authors.lastname: Brecha
authors.affiliation: Department of Neurobiology and Jules Stein Eye Institute, David Geffen School of Medicine, University of California, Los Angeles, California; Department of Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California; and Department of Physiology and Biophysics and Department of Ophthalmology and Visual Sciences, Dalhousie University, Halifax, Nova Scotia, Canada sbarnes@dal.ca.
authors.forename: Steven
authors.initials: S
authors.lastname: Barnes
mesh_terms: D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D055592:Biophysical Phenomena / Q000187:drug effects / Q000235:genetics; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D017630:Connexins / Q000235:genetics / Q000378:metabolism; D004298:Dopamine / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D037121:Plant Lectins / Q000235:genetics / Q000378:metabolism; D022661:RNA, Untranslated / Q000235:genetics / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D012160:Retina / Q000166:cytology; D051248:Retinal Horizontal Cells / Q000187:drug effects / Q000502:physiology*; D013134:Spiperone / Q000494:pharmacology; D020866:omega-Conotoxin GVIA / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D017630:Connexins; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; C119811:Gja10 protein, mouse; C110853:Gt(ROSA)26Sor non-coding RNA, mouse; D037121:Plant Lectins; D022661:RNA, Untranslated; D017447:Receptors, Dopamine D1; C034981:tomato lectin; D013134:Spiperone; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D020866:omega-Conotoxin GVIA; D002118:Calcium; D004298:Dopamine
keywords: Ca channels; Ca2+ currents; G protein βγ-subunit; inhibition; retinal horizontal cells