title: Functional coupling between heterologously expressed dopamine D(2) receptors and KCNQ channels.
abstract: Activation of KCNQ potassium channels by stimulation of co-expressed dopamine D(2) receptors was studied electrophysiologically in Xenopus laevis oocytes and in mammalian cells. To address the specificity of the interaction between D(2)-like receptors and KCNQ channels, combinations of KCNQ1-5 channels and D(2)-like receptors (D(2L), D(3), and D(4)) were investigated in Xenopus oocytes. Activation of either receptor with the selective D(2)-like receptor agonist quinpirole (100 nM) stimulated all the KCNQ currents, independently of the subunit combination, indicating a common pathway of receptor-channel interaction. The KCNQ4 current was investigated in further detail and was increased by 19.9+/-1.6% ( n=20) by D(2L) receptor stimulation. The effect could be mimicked by injection of GTPgammaS and prevented by injection of Bordetella pertussis toxin, indicating that channel stimulation was mediated via a G protein of the G(alphai/o) subtype. Cells of the human neuroblastoma line SH-SY5Y were co-transfected transiently with KCNQ4 and D(2L) receptors. Stimulation of D(2L) receptors increased the KCNQ4 current ( n=6) as determined in whole-cell patch-clamp recordings. The specificity of the dopaminergic activation of the KCNQ channels was confirmed by co-expression of other neuronal K(+) channels (BK, K(V)1.1, and K(V)4.3) with the D(2L) receptor in Xenopus oocytes. None of these K(+) channels responded to stimulation of the D(2L) receptor. In the mammalian brain, dopamine D(2) receptors and KCNQ channels co-localise postsynaptically in several brain regions, so modulation of neuronal excitability by dopamine release could in part be mediated via an effect on KCNQ channels.
authors.affiliation: Department of Medical Physiology, The Panum Institute, University of Copenhagen, Blegdamsvej 3C, Building 12.5, 2200, Copenhagen N, Denmark.
authors.forename: Trine
authors.initials: T
authors.lastname: Ljungstrom
authors.forename: Morten
authors.initials: M
authors.lastname: Grunnet
authors.forename: Bo Skaaning
authors.initials: BS
authors.lastname: Jensen
authors.forename: Søren-Peter
authors.initials: SP
authors.lastname: Olesen
mesh_terms: D000818:Animals; D001711:Biotransformation / Q000187:drug effects; D001932:Brain Neoplasms / Q000378:metabolism; D045744:Cell Line, Tumor; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D018491:Dopamine Agonists / Q000494:pharmacology; D004594:Electrophysiology; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000502:physiology; D009447:Neuroblastoma / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009865:Oocytes / Q000378:metabolism; D018408:Patch-Clamp Techniques; D037342:Pertussis Toxin / Q000494:pharmacology; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014982:Xenopus laevis
chemical_list: D018076:DNA, Complementary; D018491:Dopamine Agonists; D015221:Potassium Channels; D017448:Receptors, Dopamine D2; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D037342:Pertussis Toxin