title: Role of domain I of neuronal Ca2+ channel alpha1 subunits in G protein modulation.
abstract: 1. We studied the G protein inhibition of heteromultimeric neuronal Ca2+ channels by constructing a series of chimeric channels between the strongly modulated alpha1B subunit and the alpha1E(rbEII) subunit, which showed no modulation. 2. In parallel studies, alpha1 subunit constructs were co-expressed together with the accessory Ca2+ channel alpha2-delta and beta2a subunits in mammalian (COS-7) cells and Xenopus oocytes. G protein inhibition of expressed Ca2+ channel currents was induced by co-transfection of Gbeta1 and Ggamma2 subunits in COS-7 cells or activation of co-expressed dopamine (D2) receptors by quinpirole (100 nM) in oocytes. 3. The data indicate that transfer of the alpha1B region containing the N-terminal, domain I and the I-II loop (i.e. the alpha1B1-483 sequence), conferred G protein modulation on alpha1E(rbEII), both in terms of a slowing of activation kinetics and a reduction in current amplitude. 4. In contrast, the data are not consistent with the I-II loop and/or the C-terminal forming a unique site for G protein modulation.
authors.affiliation: Department of Pharmacology, University College London, London WC1E 6BT, UK. g.stephens@ucl.ac.uk
authors.forename: G J
authors.initials: GJ
authors.lastname: Stephens
authors.forename: C
authors.initials: C
authors.lastname: Cantí
authors.forename: K M
authors.initials: KM
authors.lastname: Page
authors.forename: A C
authors.initials: AC
authors.lastname: Dolphin
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002417:Cattle; D002460:Cell Line; D004558:Electric Stimulation; D004594:Electrophysiology; D019204:GTP-Binding Proteins / Q000235:genetics / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology; D008969:Molecular Sequence Data; D009474:Neurons / Q000502:physiology*; D009865:Oocytes / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011817:Rabbits; D051381:Rats; D014162:Transfection; D014982:Xenopus laevis
chemical_list: D015220:Calcium Channels; D019204:GTP-Binding Proteins