G beta 2 mimics activation kinetic slowing of CaV2.2 channels by noradrenaline in rat sympathetic neurons

• Published in: Biochemical and biophysical research communications Vol. 445; no. 1; pp. 250 - 254
• Main Authors: Hernandez-Castellanos, Juan M, Vivas, Oscar, Garduno, Julieta, De la Cruz, Lizbeth, Arenas, Isabel, Elias-Vinas, David, Mackie, Ken, Garcia, David E
• Format: Journal Article
• Language: English
• Published: 01.02.2014
• ISSN: 0006-291X
• DOI: 10.1016/j.bbrc.2014.01.192

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 G beta 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 G beta 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 G beta subunits and found that G beta 2 mimics activation kinetic slowing of CaV2.2 channels by noradrenaline. Furthermore, overexpression of the G beta 2 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.