Channelpedia

PubMed 24513289


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Cav2.2 , Slo1



Title: Gβ₂ mimics activation kinetic slowing of CaV2.2 channels by noradrenaline in rat sympathetic neurons.

Authors: Juan M Hernández-Castellanos, Oscar Vivas, Julieta Garduño, Lizbeth De la Cruz, Isabel Arenas, David Elías-Viñas, Ken Mackie, David E García

Journal, date & volume: Biochem. Biophys. Res. Commun., 2014 Feb 28 , 445, 250-4

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/24513289


Abstract
Several neurotransmitters and hormones acting through G protein-coupled receptors elicit a voltage-dependent regulation of CaV2.2 channels, having profound effects on cell function and the organism. It has been hypothesized that protein-protein interactions define specificity in signal transduction. Yet it is unknown how the molecular interactions in an intracellular signaling cascade determine the specificity of the voltage-dependent regulation induced by a specific neurotransmitter. It has been suspected that specific effector regions on the Gβ subunits of the G proteins are responsible for voltage-dependent regulation. The present study examines whether a neurotransmitter's specificity can be revealed by simple ion-current kinetic analysis likely resulting from interactions between Gβ subunits and the channel-molecule. Noradrenaline is a neurotransmitter that induces voltage-dependent regulation. By using biochemical and patch-clamp methods in rat sympathetic neurons we examined calcium current modulation induced by each of the five Gβ subunits and found that Gβ2 mimics activation kinetic slowing of CaV2.2 channels by noradrenaline. Furthermore, overexpression of the Gβ2 isoform reproduces the effect of noradrenaline in the willing-reluctant model. These results advance our understanding on the mechanisms by which signals conveying from a variety of membrane receptors are able to display precise homeostatic responses.