Electrical Communication in Lymphangions
Electrical Communication in Lymphangions
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DOI：
10.1016/j.bpj.2018.07.033
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发表时间：
2018-09-04
影响因子：
3.4
通讯作者：
Davis, Michael John
中科院分区：
文献类型：
--
作者：
Hald, Bjorn Olav;Castorena-Gonzalez, Jorge Augusto;Davis, Michael John
淋巴管的收缩，即两个单向淋巴瓣之间的节段，产生压力梯度，推动淋巴回到循环。每个淋巴管由一层或多层淋巴肌细胞(LMC)包围的淋巴管内皮细胞构成。每一次收缩都是由LMC动作电位(AP)产生的，该动作电位通过沿淋巴管的缝隙连接传播。然而，细胞层内和细胞层之间的电耦合以及对AP波的影响还知之甚少。在这里，我们将大鼠和小鼠淋巴管的研究与数学模型相结合，表明AP波的启动取决于高输入电阻(低电流漏)，而传播取决于形态和足够的LMC：LMC耦合。模拟结果表明：1)肌内皮细胞偶联对AP的产生和维持25 mV的实验测量的交叉连接电势差并不显著，即AP波仅沿LMC层传播；2)LMC：LMC阻力估计在2-10 MQ左右，但取决于血管结构和细胞-细胞耦合，例如，一定程度的LMC重叠保护AP波不受LMC去耦合的影响；3)AP波在瓣膜附近最容易启动，那里LMC密度较低；4)嵌入LMC层的单个起搏器单元必须能够产生非常大的电流，以克服来自该层的电流消耗。然而，在刺激多个相邻的LMC时，启动AP波所需的电流产生减少。在刺激所有LMC的情况下，AP波也可以由LMC电活动的异质性引起。这些发现促进了我们对在LMC层启动AP的电学约束的理解，并对形态、LMC兴奋性和LMC：LMC电耦合如何相互作用来确定在小淋巴管中启动和传播AP波的能力进行了可检验的预测。
Contractions of lymphangions, i.e., the segment between two one-way lymphatic valves, generate the pressure gradients that propel lymph back to the circulation. Each lymphangion is comprised of an inner sheet of lymphatic endothelial cells circumscribed by one or more layers of lymphatic muscle cells (LMCs). Each contraction is produced by an LMC action potential (AP) that propagates via gap junctions along the lymphangion. Yet, electrical coupling within and between cell layers and the impact on AP waves is poorly understood. Here, we combine studies in rat and mouse lymphatic vessels with mathematical modeling to show that initiation of AP waves depends on high input resistance (low current drain), whereas propagation depends on morphology and sufficient LMC:LMC coupling. Simulations show that 1) myoendothelial coupling is insignificant to facilitate AP generation and sustain an experimentally measured cross-junctional potential difference of 25 mV, i.e., AP waves propagate along the LMC layer only; 2) LMC:LMC resistance is estimated around 2-10 MQ but depends on vessel structure and cell-cell coupling, e.g., some degree of LMC overlap protects AP waves against LMC decoupling; 3) the propensity of AP wave initiation is highest around the valves, where the density of LMCs is low; and 4) a single pacemaker cell embedded in the LMC layer must be able to generate very large currents to overcome the current drain from the layer. However, the required current generation to initiate an AP wave is reduced upon stimulation of multiple adjacent LMCs. With stimulation of all LMCs, AP waves can also arise from heterogeneity in the electrical activity of LMCs. The findings advance our understanding of the electrical constraints that underlie initiation of APs in the LMC layer and make testable predictions about how morphology, LMC excitability, and LMC:LMC electrical coupling interact to determine the ability to initiate and propagate AP waves in small lymphatic vessels.