title: Interaction between G proteins and accessory subunits in the regulation of 1B calcium channels in Xenopus oocytes.
abstract: The accessory beta subunits of voltage-dependent Ca2+ channels (VDCCs) have been shown to regulate their biophysical properties and have also been suggested to antagonise the G protein inhibition of N-type (alpha1B), P/Q-type (alpha1A) and alpha1E channels. Here we have examined the voltage-dependent involvement of the four neuronal isoforms (beta1b, beta2a, beta3 and beta4) in the process of G protein modulation of alpha1B Ca2+ channels. All beta subunits hyperpolarized alpha1B current activation, and all antagonised the G protein-mediated depolarisation of current activation. However, except in the case of beta2a, there was no generalised reduction by beta subunits in the maximal extent of receptor-mediated inhibition of alpha1B current. In addition, all VDCC beta subunits enhanced the rate of current facilitation at +100 mV, for both receptor-mediated and tonic modulation. The rank order for enhancement of facilitation rate was beta3 > beta4 > beta1b > beta2a. In contrast, the amount of voltage-dependent facilitation during tonic modulation was reduced by beta subunit co-expression, despite the fact that the apparent Gbetagamma dissociation rate at +100 mV was enhanced by beta subunits to a similar level as for agonist-induced modulation. Our data provide evidence that G protein activation antagonises Ca2+-channel beta subunit-induced hyperpolarisation of current activation. Conversely, co-expression of all beta subunits increases the apparent Gbetagamma dimer dissociation rate during a depolarising prepulse. This latter feature suggests the co-existence of bound Ca2+-channel beta subunits and Gbetagamma dimers on the alpha1B subunits. Future work will determine how the interaction between Gbetagamma dimers and Ca2+-channel beta subunits with alpha1B results in a functional antagonism at the molecular level.
authors.affiliation: Department of Pharmacology, University College London, Gower Street, London WC1E 6BT, UK. c.canti@ucl.ac.uk
authors.forename: C
authors.initials: C
authors.lastname: Cantí
authors.forename: Y
authors.initials: Y
authors.lastname: Bogdanov
authors.forename: A C
authors.initials: AC
authors.lastname: Dolphin
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000235:genetics; D018491:Dopamine Agonists / Q000494:pharmacology; D004594:Electrophysiology; D019204:GTP-Binding Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007700:Kinetics; D008564:Membrane Potentials / Q000502:physiology; D009865:Oocytes / Q000378:metabolism; D018408:Patch-Clamp Techniques; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D014982:Xenopus laevis
chemical_list: D015220:Calcium Channels; D018491:Dopamine Agonists; D017448:Receptors, Dopamine D2; D019257:Quinpirole; D004247:DNA; D019204:GTP-Binding Proteins