Interaction between G proteins and accessory β subunits in the regulation of α1B calcium channels in Xenopus oocytes

Publisher Website
Google Scholar
Abstract
The accessory β 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 (α1B), P/Q-type (α1A) and α1E channels. Here we have examined the voltage-dependent involvement of the four neuronal isoforms (β1b, β2a, β3 and β4) in the process of G protein modulation of α1B Ca2+ channels. All β subunits hyperpolarised α1B current activation, and all antagonised the G protein-mediated depolarisation of current activation. However, except in the case of β2a, there was no generalised reduction by β subunits in the maximal extent of receptor-mediated inhibition of α1B current. In addition, all VDCC β 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 β3 > β4 > β1b > β2a. In contrast, the amount of voltage-dependent facilitation during tonic modulation was reduced by β subunit co-expression, despite the fact that the apparent Gβγ dissociation rate at +100 mV was enhanced by β subunits to a similar level as for agonist-induced modulation. Our data provide evidence that G protein activation antagonises Ca2+-channel β subunit-induced hyperpolarisation of current activation. Conversely, co-expression of all β subunits increases the apparent Gβγ dimer dissociation rate during a depolarising prepulse. This latter feature suggests the co-existence of bound Ca2+-channel β subunits and Gβγ dimers on the α1B subunits. Future work will determine how the interaction between Gβγ dimers and Ca2+-channel β subunits with α1B results in a functional antagonism at the molecular level.