Alpha7-nicotinic acetylcholine receptor subunit is not required for parasympathetic control of the heart in the mouse

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 alpha(7)-subunit for parasympathetic innervation of the heart. Normal (C57BL/6J), (alpha 7)-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, wildtype, and Chrna7 mice. VS showed no difference between control and Chrna7 mice throughout the range of stimulation (5 - 20 Hz). Mice deficient in the (alpha 7)-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 (alpha 7)-deficient mice. These data support previous findings in vitro and highlight the important differences in function between nicotinic receptor subtypes because (alpha 3)-deficient mice display major autonomic dysfunction. We conclude that the (alpha 7)-subunit does not contribute critically to resting parasympathetic control of the heart.