α7-Nicotinic acetylcholine receptor subunit is not required for parasympathetic control of the heart in the mouse
α7-Nicotinic acetylcholine receptor subunit is not required for parasympathetic control of the heart in the mouse
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DOI：
10.1152/physiolgenomics.00085.2004
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发表时间：
2005-06-16
影响因子：
4.6
通讯作者：
Dunlap, ME
中科院分区：
文献类型：
--
作者：
Deck, J;Bibevski, S;Dunlap, ME
烟碱型乙酰胆碱受体（nAChR）是由9个α亚基和3个β亚基组成的功能性五聚体。不同的亚基的贡献，天然的，生理上重要的nAChR在自主神经节的突触传递尚不清楚。在这里，我们研究了α（7）-亚基对心脏副交感神经支配的重要性。正常（C57 BL/6 J）、（α 7）缺陷（Chrna 7）和野生型同窝小鼠植入遥测装置，在清醒、未镇静条件下，在基线和阿托品、普萘洛尔和溴化六甲双铵给药后获得ECG记录。进行心率变异性的频谱分析[功率谱分析（PSA）]，以评价心脏的静息自主神经张力。在完成意识研究时，将动物麻醉并进行迷走神经（VS）的电刺激，同时记录R-R间期。所有三组动物的基线心率和阿托品、普萘洛尔或六烃季铵给药后的心率相似。PSA曲线在正常、野生型和Chrna 7小鼠之间相似。VS显示在整个刺激范围（5 - 20 Hz）内，对照和Chrna 7小鼠之间没有差异。缺乏（α 7）-nAChR亚单位的小鼠在基线或单一和联合自主神经阻滞条件下，心脏静息自主神经张力没有显示差异。VS显示正常和（α 7）缺陷小鼠之间的心率反应没有差异。这些数据支持以前的研究结果在体外，并强调烟碱受体亚型之间的功能的重要差异，因为（α 3）-缺陷小鼠显示主要的自主神经功能障碍。我们的结论是（α 7）-亚基并没有作出重大贡献，休息副交感神经控制的心脏。
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.