Kapela Adam, Behringer Erik J, Segal Steven S, Tsoukias Nikolaos M
Department of Biomedical Engineering, Florida International University, Miami, FL, USA.
Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, MO, USA.
Microcirculation. 2018 Feb;25(2). doi: 10.1111/micc.12429.
Electrical signaling along the endothelium underlies spreading vasodilation and blood flow control. We use mathematical modeling to determine the electrical properties of the endothelium and gain insight into the biophysical determinants of electrical conduction.
Electrical conduction data along endothelial tubes (40 μm wide, 2.5 mm long) isolated from mouse skeletal muscle resistance arteries were analyzed using cable equations and a multicellular computational model.
Responses to intracellular current injection attenuate with an axial length constant (λ) of 1.2-1.4 mm. Data were fitted to estimate the axial (r ; 10.7 MΩ/mm) and membrane (r ; 14.5 MΩ∙mm) resistivities, EC membrane resistance (R ; 12 GΩ), and EC-EC coupling resistance (R ; 4.5 MΩ) and predict that stimulation of ≥30 neighboring ECs is required to elicit 1 mV of hyperpolarization at distance = 2.5 mm. Opening Ca -activated K channels (K ) along the endothelium reduced λ by up to 55%.
High R makes the endothelium sensitive to electrical stimuli and able to conduct these signals effectively. Whereas the activation of a group of ECs is required to initiate physiologically relevant hyperpolarization, this requirement is increased by myoendothelial coupling and K activation along the endothelium inhibits conduction by dissipating electrical signals.
内皮细胞上的电信号是血管舒张扩展和血流控制的基础。我们使用数学建模来确定内皮细胞的电特性,并深入了解电传导的生物物理决定因素。
使用电缆方程和多细胞计算模型分析从小鼠骨骼肌阻力动脉分离的内皮管(宽40μm,长2.5mm)上的电传导数据。
对细胞内电流注入的反应以1.2 - 1.4mm的轴向长度常数(λ)衰减。通过数据拟合来估计轴向电阻率(r;10.7MΩ/mm)和膜电阻率(r;14.5MΩ∙mm)、内皮细胞膜电阻(R;12GΩ)以及内皮细胞 - 内皮细胞耦合电阻(R;4.5MΩ),并预测在距离 = 2.5mm处引发1mV超极化需要刺激≥30个相邻的内皮细胞。沿内皮细胞开放钙激活钾通道(K)可使λ降低多达55%。
高R值使内皮细胞对电刺激敏感,并能够有效地传导这些信号。虽然需要一组内皮细胞被激活才能引发生理相关的超极化,但这种需求会因肌内皮耦合而增加,并且沿内皮细胞的K激活会通过耗散电信号来抑制传导。