Adam Kapela1, Erik J Behringer2,3, Steven S Segal2,4, Nikolaos M Tsoukias1,5. 1. Department of Biomedical Engineering, Florida International University, Miami, FL, USA. 2. Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, MO, USA. 3. Department of Basic Sciences, Loma Linda University, Loma Linda, CA, USA. 4. Dalton Cardiovascular Research Center, University of Missouri, Columbia, MO, USA. 5. School of Chemical Engineering, National Technical University of Athens, Athens, Greece.
Abstract
OBJECTIVE: 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. METHODS: 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. RESULTS: 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 (ra ; 10.7 MΩ/mm) and membrane (rm ; 14.5 MΩ∙mm) resistivities, EC membrane resistance (Rm ; 12 GΩ), and EC-EC coupling resistance (Rgj ; 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 Ca2+ -activated K+ channels (KCa ) along the endothelium reduced λ by up to 55%. CONCLUSIONS: High Rm 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 KCa activation along the endothelium inhibits conduction by dissipating electrical signals.
OBJECTIVE: 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. METHODS: 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. RESULTS: 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 (ra ; 10.7 MΩ/mm) and membrane (rm ; 14.5 MΩ∙mm) resistivities, EC membrane resistance (Rm ; 12 GΩ), and EC-EC coupling resistance (Rgj ; 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 Ca2+ -activated K+ channels (KCa ) along the endothelium reduced λ by up to 55%. CONCLUSIONS: High Rm 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 KCa activation along the endothelium inhibits conduction by dissipating electrical signals.
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