Hald Bjørn Olav, Jacobsen Jens Christian Brings, Sandow Shaun L, Holstein-Rathlou Niels-Henrik, Welsh Donald G
Department of Biomedical Sciences, University of Copenhagen, Denmark
Department of Biomedical Sciences, University of Copenhagen, Denmark.
J Physiol. 2014 Aug 1;592(15):3243-55. doi: 10.1113/jphysiol.2014.272815. Epub 2014 Jun 6.
Dysfunctional electrical signalling within the arteriolar wall is a major cause of cardiovascular disease. The endothelial cell layer constitutes the primary electrical pathway, co-ordinating contraction of the overlying smooth muscle cell (SMC) layer. As myoendothelial gap junctions (MEGJs) provide direct contact between the cell layers, proper vasomotor responses are thought to depend on a high, uniform MEGJ density. However, MEGJs are observed to be expressed heterogeneously within and among vascular beds. This discrepancy is addressed in the present study. As no direct measures of MEGJ conductance exist, we employed a computational modelling approach to vary the number, conductance and distribution of MEGJs. Our simulations demonstrate that a minimal number of randomly distributed MEGJs augment arteriolar cell-cell communication by increasing conduction efficiency and ensuring appropriate membrane potential responses in SMCs. We show that electrical coupling between SMCs must be tailored to the particular MEGJ distribution. Finally, observation of non-decaying mechanical conduction in arterioles without regeneration has been a long-standing controversy in the microvascular field. As heterogeneous MEGJ distributions provide for different conduction profiles along the cell layers, we demonstrate that a non-decaying conduction profile is possible in the SMC layer of a vessel with passive electrical properties. These intriguing findings redefine the concept of efficient electrical communication in the microcirculation, illustrating how heterogeneous properties, ubiquitous in biological systems, may have a profound impact on system behaviour and how acute local and global flow control is explained from the biophysical foundations.
小动脉壁内功能失调的电信号传导是心血管疾病的主要原因。内皮细胞层构成主要的电通路，协调上方平滑肌细胞（SMC）层的收缩。由于肌内皮间隙连接（MEGJ）提供了细胞层之间的直接接触，适当的血管舒缩反应被认为取决于高且均匀的MEGJ密度。然而，观察发现MEGJ在血管床内和血管床之间呈异质性表达。本研究探讨了这一差异。由于不存在对MEGJ电导的直接测量方法，我们采用计算建模方法来改变MEGJ的数量、电导和分布。我们的模拟表明，最少数量的随机分布的MEGJ通过提高传导效率和确保SMC中适当的膜电位反应来增强小动脉细胞间通讯。我们表明，SMC之间的电耦合必须根据特定的MEGJ分布进行调整。最后，在没有再生的小动脉中观察到非衰减性机械传导一直是微血管领域长期存在的争议。由于异质性MEGJ分布沿细胞层提供不同的传导模式，我们证明在具有被动电特性的血管的SMC层中可能存在非衰减性传导模式。这些有趣的发现重新定义了微循环中有效电通讯的概念，说明了生物系统中普遍存在的异质性特性如何可能对系统行为产生深远影响，以及如何从生物物理基础解释急性局部和全局血流控制。
