title: Alpha7-nicotinic acetylcholine receptor subunit is not required for parasympathetic control of the heart in the mouse.
abstract: Nicotinic acetylcholine receptors (nAChR) are assembled from a pool of nine alpha-subunits and three beta-subunits into functional pentamers in peripheral autonomic neurons. The contribution of different subunits to native, physiologically important nAChR for synaptic transmission in autonomic ganglia is unclear. Here, we examined the importance of the alpha7-subunit for parasympathetic innervation of the heart. Normal (C57BL/6J), alpha7-deficient (Chrna7), and wild-type littermate mice were implanted with telemetry devices, and, under conscious, unsedated conditions, ECG recordings were obtained at baseline and after atropine, propranolol, and hexamethonium bromide administration. Spectral analysis of heart rate variability [power spectral analysis (PSA)] was performed for the evaluation of resting autonomic tone to the heart. At the completion of conscious studies, animals were anesthetized and underwent electrical stimulation of the vagus nerve (VS) while R-R intervals were recorded. Heart rate at baseline and after atropine, propranolol, or hexamethonium was similar in all three groups of animals. PSA curves were similar between normal, wild-type, and Chrna7 mice. VS showed no difference between control and Chrna7 mice throughout the range of stimulation (5-20 Hz). Mice deficient in the alpha7-nAChR subunit do not display differences in resting autonomic tone to the heart at baseline or under conditions of single and combined autonomic blockade. VS showed no difference in heart rate responses between normal and alpha7-deficient mice. These data support previous findings in vitro and highlight the important differences in function between nicotinic receptor subtypes because alpha3-deficient mice display major autonomic dysfunction. We conclude that the alpha7-subunit does not contribute critically to resting parasympathetic control of the heart.
authors.affiliation: Department of Veterans Affairs Medical Center, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Deck
authors.forename: Steve
authors.initials: S
authors.lastname: Bibevski
authors.forename: Tomaso
authors.initials: T
authors.lastname: Gnecchi-Ruscone
authors.forename: Valentina
authors.initials: V
authors.lastname: Bellina
authors.forename: Nicola
authors.initials: N
authors.lastname: Montano
authors.forename: Mark E
authors.initials: ME
authors.lastname: Dunlap
mesh_terms: D000818:Animals; D001285:Atropine / Q000494:pharmacology; D004558:Electric Stimulation; D006321:Heart / Q000294:innervation* / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects; D018738:Hexamethonium / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010275:Parasympathetic Nervous System / Q000378:metabolism*; D011433:Propranolol / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000378:metabolism*; D014630:Vagus Nerve / Q000187:drug effects; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: C579166:Chrna7 protein, mouse; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D018738:Hexamethonium; D001285:Atropine; D011433:Propranolol