XB-ART-10323J Physiol September 15, 2000; 527 Pt 3 419-32.
Interaction between G proteins and accessory subunits in the regulation of 1B calcium channels in Xenopus oocytes.
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.
PubMed ID: 10990530
PMC ID: PMC2270102
Article link: J Physiol
References [+] :
Bourinet, Determinants of the G protein-dependent opioid modulation of neuronal calcium channels. 1996, Pubmed, Xenbase