Physiologic regulation of heart rate and blood pressure involves connexin 36-containing gap junctions.
Physiologic regulation of heart rate and blood pressure involves connexin 36-containing gap junctions.
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心率和血压的生理调节涉及连接36的间隙连接。
DOI：
10.1096/fj.201600919rr
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发表时间：
2017-09
期刊：
影响因子：
--
通讯作者：
Deuchars SA
中科院分区：
文献类型：
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作者：
Lall VK;Bruce G;Voytenko L;Drinkhill M;Wellershaus K;Willecke K;Deuchars J;Deuchars SA
长期升高的交感神经活动是许多心血管疾病的基础。阐明交感神经系统输出的机制可能会揭示新的治疗途径。使用具有特定 Cx36 基因缺失的小鼠测定间隙连接蛋白连接蛋白 36 (Cx36) 对交感神经活动调节以及血压和心率的贡献。在 Cx36 敲除 (KO) 小鼠的交感神经节前神经元中证实了 Cx36 蛋白的消融。对有意识的 Cx36 KO 小鼠的遥测分析显示，与野生型 (WT) 小鼠相比，在休息和活动期间心率和血压的差异更大，并且麻醉时对化学感受器激活的反应较小。与 WT 小鼠相比，在 Cx36-KO 小鼠的工作心脑干制备中，呼吸耦合交感神经放电减弱，对化学感受器刺激和有害刺激的反应减弱。使用全细胞贴片记录，与 WT 小鼠相比，Cx36-KO 小鼠脊髓切片中的交感神经节前神经元显示出较低水平的小穗活性，表明神经元之间的间隙连接耦合减少。因此，Cx36 缺失会破坏交感神经流出的正常调节，从而影响心血管参数。-Lall, V. K.、Bruce, G.、Voytenko, L.、Drinkhill, M.、Wellershaus, K.、Willecke, K.、Deuchars, J.、Deuchars, S. A. 心率和血压的生理调节涉及含有连接蛋白 36 的间隙连接。
Chronically elevated sympathetic nervous activity underlies many cardiovascular diseases. Elucidating the mechanisms contributing to sympathetic nervous system output may reveal new avenues of treatment. The contribution of the gap junctional protein connexin 36 (Cx36) to the regulation of sympathetic activity and thus blood pressure and heart rate was determined using a mouse with specific genetic deletion of Cx36. Ablation of the Cx36 protein was confirmed in sympathetic preganglionic neurons of Cx36-knockout (KO) mice. Telemetric analysis from conscious Cx36 KO mice revealed higher variance in heart rate and blood pressure during rest and activity compared to wild-type (WT) mice, and smaller responses to chemoreceptor activation when anesthetized. In the working heart–brain stem preparation of the Cx36-KO mouse, respiratory-coupled sympathetic nerve discharge was attenuated and responses to chemoreceptor stimulation and noxious stimulation were blunted compared to WT mice. Using whole cell patch recordings, sympathetic preganglionic neurons in spinal cord slices of Cx36-KO mice displayed lower levels of spikelet activity compared to WT mice, indicating reduced gap junction coupling between neurons. Cx36 deletion therefore disrupts normal regulation of sympathetic outflow with effects on cardiovascular parameters.—Lall, V. K., Bruce, G., Voytenko, L., Drinkhill, M., Wellershaus, K., Willecke, K., Deuchars, J., Deuchars, S. A. Physiologic regulation of heart rate and blood pressure involves connexin 36–containing gap junctions.