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Interaction between G proteins and accessory subunits in the regulation of 1B calcium channels in Xenopus oocytes

C. Cantí, Y. Bogdanov and A. C. Dolphin

1. The accessory 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 (1B), P/Q-type (1A) and 1E channels. Here we have examined the voltage-dependent involvement of the four neuronal isoforms (1b, 2a, 3 and 4) in the process of G protein modulation of 1B Ca²⁺ channels.

2. All subunits hyperpolarised 1B current activation, and all antagonised the G protein-mediated depolarisation of current activation. However, except in the case of 2a, there was no generalised reduction by subunits in the maximal extent of receptor-mediated inhibition of 1B current.

3. In addition, all VDCC 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 3 > 4 > 1b > 2a. In contrast, the amount of voltage-dependent facilitation during tonic modulation was reduced by subunit co-expression, despite the fact that the apparent G dissociation rate at +100 mV was enhanced by subunits to a similar level as for agonist-induced modulation.

4. Our data provide evidence that G protein activation antagonises Ca²⁺-channel subunit-induced hyperpolarisation of current activation. Conversely, co-expression of all subunits increases the apparent G dimer dissociation rate during a depolarising prepulse. This latter feature suggests the co-existence of bound Ca²⁺-channel subunits and G dimers on the 1B subunits. Future work will determine how the interaction between G dimers and Ca²⁺-channel subunits with 1B results in a functional antagonism at the molecular level.

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