Sturdy Jacob, Ottesen Johnny T, Olufsen Mette S
Department of Structural Engineering, Norwegian University of Science and Technology, Richard Birkelandsvei 1A, 7491, Trondheim, Norway.
Department of Science and Environment, Roskilde University, Universitetsvej 1, 4000, Roskilde, Denmark.
J Comput Neurosci. 2017 Feb;42(1):11-30. doi: 10.1007/s10827-016-0624-6. Epub 2016 Oct 5.
The baroreceptor neurons serve as the primary transducers of blood pressure for the autonomic nervous system and are thus critical in enabling the body to respond effectively to changes in blood pressure. These neurons can be separated into two types (A and C) based on the myelination of their axons and their distinct firing patterns elicited in response to specific pressure stimuli. This study has developed a comprehensive model of the afferent baroreceptor discharge built on physiological knowledge of arterial wall mechanics, firing rate responses to controlled pressure stimuli, and ion channel dynamics within the baroreceptor neurons. With this model, we were able to predict firing rates observed in previously published experiments in both A- and C-type neurons. These results were obtained by adjusting model parameters determining the maximal ion-channel conductances. The observed variation in the model parameters are hypothesized to correspond to physiological differences between A- and C-type neurons. In agreement with published experimental observations, our simulations suggest that a twofold lower potassium conductance in C-type neurons is responsible for the observed sustained basal firing, where as a tenfold higher mechanosensitive conductance is responsible for the greater firing rate observed in A-type neurons. A better understanding of the difference between the two neuron types can potentially be used to gain more insight about pathophysiology and treatment of diseases related to baroreflex function, e.g. in patients with autonomic failure, a syndrome that is difficult to diagnose in terms of its pathophysiology.
压力感受器神经元是自主神经系统中血压的主要传感器，因此对于使身体能够有效应对血压变化至关重要。这些神经元可根据其轴突的髓鞘形成以及对特定压力刺激产生的不同放电模式分为两种类型（A 型和 C 型）。本研究基于动脉壁力学的生理学知识、对受控压力刺激的放电频率反应以及压力感受器神经元内的离子通道动力学，开发了一个全面的传入压力感受器放电模型。利用这个模型，我们能够预测先前发表的实验中在 A 型和 C 型神经元中观察到的放电频率。这些结果是通过调整决定最大离子通道电导的模型参数获得的。模型参数中观察到的变化被假设为对应于 A 型和 C 型神经元之间的生理差异。与已发表的实验观察结果一致，我们的模拟表明，C 型神经元中钾电导降低两倍导致了观察到的持续基础放电，而机械敏感性电导高十倍则导致了 A 型神经元中观察到的更高放电频率。更好地理解这两种神经元类型之间的差异可能有助于更深入地了解与压力反射功能相关疾病的病理生理学和治疗方法，例如在自主神经功能衰竭患者中，这种综合征在病理生理学方面难以诊断。
