A model of cellular cardiac-neural coupling that captures the sympathetic control of sinoatrial node excitability in normotensive and hypertensive rats.

A model of cellular cardiac-neural coupling that captures the sympathetic control of sinoatrial node excitability in normotensive and hypertensive rats.
复制标题

细胞心脏-神经耦合模型,捕捉正常血压和高血压大鼠窦房结兴奋性的交感神经控制。

DOI:
10.1016/j.bpj.2011.05.069
复制
发表时间:
2011
影响因子:
3.4
通讯作者:
Tao T
Tao T
中科院分区:
生物学3区
文献类型:
--
作者:
Tao T

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高血压与交感神经亢进有关。为了表示这种神经-肌细胞耦合,并阐明心脏起搏器交感控制的机制,我们开发了一种新的(据我们所知)细胞数学模型,该模型结合了正常血压(WKY)和高血压(SHR)大鼠交感静脉曲张和窦房结(SAN)之间细胞间通讯的信号信息。该模型的特点包括1)、具有特定离子通道功能和Ca2+处理元件的起搏器活动的描述; 2)、SAN激发的动态β-肾上腺素能调节; 3)、用NE释放动力学表示交感静脉曲张的离子活性; 4)、将静脉曲张模型与 SAN 模型耦合以模拟突触前递质释放驱动突触后兴奋性。该框架捕获了神经-肌细胞耦合以及一氧化氮和环鸟苷酸对起搏的调节。它还再现了对短暂交感神经刺激的变时性反应。最后,SHR 模型定量表明,交感裂两侧环 GMP 调节的受损对于高血压中观察到的自主神经表型的发展至关重要。
Hypertension is associated with sympathetic hyperactivity. To represent this neural-myocyte coupling, and to elucidate the mechanisms underlying sympathetic control of the cardiac pacemaker, we developed a new (to our knowledge) cellular mathematical model that incorporates signaling information from cell-to-cell communications between the sympathetic varicosity and sinoatrial node (SAN) in both normotensive (WKY) and hypertensive (SHR) rats. Features of the model include 1), a description of pacemaker activity with specific ion-channel functions and Ca2+handling elements; 2), dynamicβ-adrenergic modulation of the excitation of the SAN; 3), representation of ionic activity of sympathetic varicosity with NE release dynamics; and 4), coupling of the varicosity model to the SAN model to simulate presynaptic transmitter release driving postsynaptic excitability. This framework captures neural-myocyte coupling and the modulation of pacemaking by nitric oxide and cyclic GMP. It also reproduces the chronotropic response to brief sympathetic stimulations. Finally, the SHR model quantitatively suggests that the impairment of cyclic GMP regulation at both sides of the sympathetic cleft is crucial for development of the autonomic phenotype observed in hypertension.
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