Deletion of neurturin impairs development of cholinergic nerves and heart rate control in postnatal mouse hearts
Deletion of neurturin impairs development of cholinergic nerves and heart rate control in postnatal mouse hearts
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DOI：
10.14814/phy2.12779
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发表时间：
2016-05-01
影响因子：
2.5
通讯作者：
Hoover, Donald B.
中科院分区：
文献类型：
--
作者：
Downs, Anthony M.;Jalloh, Hawa B.;Hoover, Donald B.
成年小鼠心脏的正常胆碱能神经支配和对迷走神经刺激的心动过缓反应需要神经营养因子Neurturin。我们的目标是确定神经肽缺失对出生后小鼠心脏变时性和变流性功能、迷走神经压力感受性反射反应和结节区胆碱能神经密度的影响。实验在出生后C57BL/6野生型(WT)和神经突蛋白基因敲除(KO)小鼠上进行。使用ECGenie仪器无创地记录清醒幼鼠的连续心电。用阿替洛尔评价和阻断交感神经对心率(HR)和苯肾上腺素(PE)刺激压力感受器反射的影响。石蜡切片用免疫组织化学方法标记胆碱能神经。WT和KO小鼠在出生后2.5天和21天之间表现出相似的HR增加和PR间期缩短。在P7.5，阿替洛尔治疗显著降低WT和KO仔鼠的心率。PE引起的反射性心动过缓在KO幼鼠中要小得多。P7.5KO小鼠结节区胆碱能神经密度明显减少。我们认为胆碱能神经对小鼠的HR、PR、QRS和QTC间期的发育变化影响很小。而胆碱能神经在出生后1周起介导反射性心动过缓。在出生后发育早期，神经肽缺失会损害心脏的胆碱能神经支配和压力感受器反射的迷走神经传出成分。
The neurotrophic factor neurturin is required for normal cholinergic innervation of adult mouse heart and bradycardic responses to vagal stimulation. Our goals were to determine effects of neurturin deletion on development of cardiac chronotropic and dromotropic functions, vagal baroreflex response, and cholinergic nerve density in nodal regions of postnatal mice. Experiments were performed on postnatal C57BL/6 wild-type (WT) and neurturin knockout (KO) mice. Serial electrocardiograms were recorded noninvasively from conscious pups using an ECGenie apparatus. Mice were treated with atenolol to evaluate and block sympathetic effects on heart rate (HR) and phenylephrine (PE) to stimulate the baroreflex. Immunohistochemistry was used to label cholinergic nerves in paraffin sections. WT and KO mice showed similar age-dependent increases in HR and decreases in PR interval between postnatal days (P) 2.5 and 21. Treatment with atenolol reduced HR significantly in WT and KO pups at P7.5. PE caused a reflex bradycardia that was significantly smaller in KO pups. Cholinergic nerve density was significantly less in nodal regions of P7.5 KO mice. We conclude that cholinergic nerves have minimal influence on developmental changes in HR and PR, QRS, and QTc intervals in mouse pups. However, cholinergic nerves mediate reflex bradycardia by 1 week postnatally. Deletion of neurturin impairs cholinergic innervation of the heart and the vagal efferent component of the baroreflex early during postnatal development.