title: Decay of prepulse facilitation of N type calcium channels during G protein inhibition is consistent with binding of a single Gbeta subunit.
abstract: We have examined the modulation of cloned and stably expressed rat brain N type calcium channels (alpha1B + beta1b + alpha2delta subunits) by exogenously applied purified G protein betagamma subunits. In the absence of Gbetagamma, barium currents through N type channels are unaffected by application of strong depolarizing prepulses. In contrast, inclusion of purified Gbetagamma in the patch pipette results in N type currents that initially facilitated upon application of positive prepulses followed by rapid reinhibition. Examination of the kinetics of Gbetagamma-dependent reinhibition showed that as the duration between the test pulse and the prepulse was increased, the degree of facilitation was attenuated in a monoexponential fashion. The time constant tau for the recovery from facilitation was sensitive to exogenous Gbetagamma, so that the inverse of tau linearly depended on the Gbetagamma concentration. Overall, the data are consistent with a model whereby a single Gbetagamma molecule dissociates from the channel during the prepulse, and that reassociation of Gbetagamma with the channel after the prepulse occurs as a bimolecular reaction.
authors.affiliation: Department of Pharmacology and Therapeutics, University of Calgary, 3330 Hospital Drive NW, Calgary, Canada T2N 4N1.
authors.forename: G W
authors.initials: GW
authors.lastname: Zamponi
authors.forename: T P
authors.initials: TP
authors.lastname: Snutch
mesh_terms: D000818:Animals; D001921:Brain / Q000502:physiology*; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015640:Ion Channel Gating; D018408:Patch-Clamp Techniques; D051381:Rats
chemical_list: D015220:Calcium Channels; D019204:GTP-Binding Proteins