title: Gβ₂ mimics activation kinetic slowing of CaV2.2 channels by noradrenaline in rat sympathetic neurons.
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.
authors: Department of Physiology, School of Medicine, Universidad Nacional Autónoma de México (UNAM), Apartado Postal 70250, C.P. 04510 México, D.F., México.
authors: Juan M
authors: JM
authors: Hernández-Castellanos
authors: Department of Physiology, School of Medicine, Universidad Nacional Autónoma de México (UNAM), Apartado Postal 70250, C.P. 04510 México, D.F., México.
authors: Oscar
authors: O
authors: Vivas
authors: Department of Physiology, School of Medicine, Universidad Nacional Autónoma de México (UNAM), Apartado Postal 70250, C.P. 04510 México, D.F., México.
authors: Julieta
authors: J
authors: Garduño
authors: Department of Physiology, School of Medicine, Universidad Nacional Autónoma de México (UNAM), Apartado Postal 70250, C.P. 04510 México, D.F., México.
authors: Lizbeth
authors: L
authors: De la Cruz
authors: Department of Physiology, School of Medicine, Universidad Nacional Autónoma de México (UNAM), Apartado Postal 70250, C.P. 04510 México, D.F., México.
authors: Isabel
authors: I
authors: Arenas
authors: Section of Bioelectronics, Department of Electrical Engineering, Centro de Investigación y Estudios Avanzados del Instituto Politécnico Nacional, Apartado Postal 14740, C.P. 07000 México, D.F., México.
authors: David
authors: D
authors: Elías-Viñas
authors: Department of Psychological and Brain Sciences, Gill Center for Biomedical Sciences, Indiana University, Bloomington, IN 47405, USA.
authors: Ken
authors: K
authors: Mackie
authors: Department of Physiology, School of Medicine, Universidad Nacional Autónoma de México (UNAM), Apartado Postal 70250, C.P. 04510 México, D.F., México. Electronic address: erasmo@unam.mx.
authors: David E
authors: DE
authors: García
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020864:Calcium Channels, N-Type / Q000378:metabolism*; D002478:Cells, Cultured; D044387:GTP-Binding Protein beta Subunits / Q000235:genetics / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017386:Sequence Homology, Amino Acid; D013564:Sympathetic Nervous System / Q000166:cytology; D013566:Sympathomimetics / Q000494:pharmacology
chemical_list: C503279:Cacna1b protein, rat; D020864:Calcium Channels, N-Type; D044387:GTP-Binding Protein beta Subunits; D020033:Protein Isoforms; D013566:Sympathomimetics; D049452:Green Fluorescent Proteins; D002118:Calcium; D009638:Norepinephrine
keywords: Ca(V)2.2 channel; G protein; Gβ(2) subunit; Kinetic slowing; Noradrenaline; Specificity