title: Ganglionic GFAP+glial Gq-GPCR signaling enhances heart functions in vivo.
abstract: The sympathetic nervous system (SNS) accelerates heart rate, increases cardiac contractility, and constricts resistance vessels. The activity of SNS efferent nerves is generated by a complex neural network containing neurons and glia. Gq G protein-coupled receptor (Gq-GPCR) signaling in glial fibrillary acidic protein-expressing (GFAP+) glia in the central nervous system supports neuronal function and regulates neuronal activity. It is unclear how Gq-GPCR signaling in GFAP+glia affects the activity of sympathetic neurons or contributes to SNS-regulated cardiovascular functions. In this study, we investigated whether Gq-GPCR activation in GFAP+glia modulates the regulatory effect of the SNS on the heart; transgenic mice expressing Gq-coupled DREADD (designer receptors exclusively activated by designer drugs) (hM3Dq) selectively in GFAP+glia were used to address this question in vivo. We found that acute Gq-GPCR activation in peripheral GFAP+glia significantly accelerated heart rate and increased left ventricle contraction. Pharmacological experiments suggest that the glial-induced cardiac changes were due to Gq-GPCR activation in satellite glial cells within the sympathetic ganglion; this activation led to increased norepinephrine (NE) release and beta-1 adrenergic receptor activation within the heart. Chronic glial Gq-GPCR activation led to hypotension in femaleGfap-hM3Dq mice. This study provides direct evidence that Gq-GPCR activation in peripheral GFAP+glia regulates cardiovascular functions in vivo.
authors.forename: Alison Xiaoqiao
authors.initials: AX
authors.lastname: Xie
authors.forename: Jakovin J
authors.initials: JJ
authors.lastname: Lee
authors.forename: Ken D
authors.initials: KD
authors.lastname: McCarthy
mesh_terms: D000315:Adrenalectomy; D000818:Animals; D005260:Female; D005728:Ganglia, Sympathetic / Q000166:cytology / Q000378:metabolism*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006321:Heart / Q000294:innervation*; D006339:Heart Rate; D007022:Hypotension / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009200:Myocardial Contraction; D009457:Neuroglia / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D010597:Pharmacogenetics; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D013563:Sympathectomy, Chemical; D013564:Sympathetic Nervous System / Q000378:metabolism
chemical_list: D005904:Glial Fibrillary Acidic Protein; D018342:Receptors, Adrenergic, beta-1; D043562:Receptors, G-Protein-Coupled; C528900:glial fibrillary astrocytic protein, mouse; D009638:Norepinephrine