Journal
JOURNAL OF PHYSIOLOGY-LONDON
Volume 527, Issue 3, Pages 419-432Publisher
WILEY
DOI: 10.1111/j.1469-7793.2000.t01-1-00419.x
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- Wellcome Trust Funding Source: Medline
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1. 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 (alpha 1B), P/Q-type (alpha 1A) and alpha 1E channels. Here we have examined the voltage-dependent involvement of the four neuronal isoforms (beta 1b, beta 2a, beta 3 and beta 4) in the process of G protein modulation of alpha 1B Ca2+ channels. 2. All beta subunits hyperpolarised alpha 1B current activation, and all antagonised the G-protein-mediated depolarisation of current activation. However, except in the case of beta 2a, there was no generalised reduction by beta subunits in the maximal extent of receptor-mediated inhibition of alpha 1B current. 3. 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 beta 3 > beta 4 > beta 1b > beta 2a. In contrast, the amount of voltage-dependent facilitation during tonic modulation was reduced by beta subunit co-expression, despite the fact that the apparent G beta gamma dissociation rate at +100 mV was enhanced by beta subunits to a similar level as for agonist-induced modulation. 4. 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 G beta gamma dimer dissociation rate during a depolarising prepulse. This latter feature suggests the co-existence of bound Ca2+-channel beta subunits and G beta gamma dimers on the alpha 1B subunits. Future work will determine how the interaction between G beta gamma dimers and Ca2+-channel beta subunits with alpha 1B results in a functional antagonism at the molecular level.
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