Deck Jennifer, Bibevski Steve, Gnecchi-Ruscone Tomaso, Bellina Valentina, Montano Nicola, Dunlap Mark E
Department of Veterans Affairs Medical Center, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Physiol Genomics. 2005 Jun 16;22(1):86-92. doi: 10.1152/physiolgenomics.00085.2004. Epub 2005 Mar 29.
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.
烟碱型乙酰胆碱受体(nAChR)由九个α亚基和三个β亚基组装成外周自主神经元中的功能性五聚体。不同亚基对自主神经节中用于突触传递的天然、生理上重要的nAChR的贡献尚不清楚。在此,我们研究了α7亚基对心脏副交感神经支配的重要性。将正常(C57BL/6J)、α7缺陷(Chrna7)和野生型同窝小鼠植入遥测设备,并在清醒、未使用镇静剂的条件下,在基线以及给予阿托品、普萘洛尔和溴化六甲铵后进行心电图记录。进行心率变异性的频谱分析[功率谱分析(PSA)]以评估心脏的静息自主神经张力。在清醒研究完成后,对动物进行麻醉并在记录R-R间期的同时进行迷走神经(VS)电刺激。三组动物在基线以及给予阿托品、普萘洛尔或溴化六甲铵后的心率相似。正常、野生型和Chrna7小鼠之间的PSA曲线相似。在整个刺激范围(5-20Hz)内,对照组和Chrna7小鼠的VS没有差异。缺乏α7-nAChR亚基的小鼠在基线时或在单一和联合自主神经阻滞条件下,对心脏的静息自主神经张力没有差异。正常小鼠和α7缺陷小鼠在VS心率反应上没有差异。这些数据支持了先前的体外研究结果,并突出了烟碱受体亚型之间功能上的重要差异,因为α3缺陷小鼠表现出主要的自主神经功能障碍。我们得出结论,α7亚基对心脏静息副交感神经控制没有关键作用。