A mathematical model of vasoreactivity in rat mesenteric arterioles: I. Myoendothelial communication
To study the effect of myoendothelial communication on vascular reactivity, we integrated detailed mathematical models of Ca2+ dynamics and membrane electrophysiology in arteriolar smooth muscle (SMC) and endothelial (EC) cells. Cells are coupled through the exchange of Ca2+, Cl-, K+, and Na+ ions, inositol 1,4,5-triphosphate (IP3), and the paracrine diffusion of nitric oxide (NO). EC stimulation reduces intracellular Ca2+ ([Ca2+]i) in the SMC by transmitting a hyperpolarizing current carried primarily by K+. The NO-independent endothelium-derived hyperpolarization was abolished in a synergistic-like manner by inhibition of EC SKCa and IKCa channels. During NE stimulation, IP3 diffusing from the SMC induces EC Ca2+ release, which, in turn, moderates SMC depolarization and [Ca2+]i elevation. On the contrary, SMC [Ca2+]i was not affected by EC-derived IP3. Myoendothelial Ca2+ fluxes had no effect in either cell. The EC exerts a stabilizing effect on calcium-induced calcium release-dependent SMC Ca2+ oscillations by increasing the norepinephrine concentration window for oscillations. We conclude that a model based on independent data for subcellular components can capture major features of the integrated vessel behavior. This study provides a tissue-specific approach for analyzing complex signaling mechanisms in the vasculature. Microcirculation (2009) iFirst, 1-25. doi:10.1080/10739680903177539 ADAM KAPELA 1, ANASTASIOS BEZERIANOS 2, AND NIKOLAOS M. TSOUKIAS 1 1-Department of Biomedical Engineering, Florida International University, Miami, Florida, USA; 2-University of Patras, Department of Medical Physics, Patras, Greece
Figure: Predicted Nnorepinephrine-induced and ACh-induced changes of membrane potentials (Top) and intracellular Ca2+ (Bottom) in smooth muscle cells (SMC) (solid lines) and EC (dashed red lines) coupled by the ionic and IP3 fluxes. NE stimulation depolarizes SMC and EC, and increases SMC and EC [Ca2+]i. ACh stimulation repolarizes EC and SMC, increases EC [Ca2+]i, and reduces SMC [Ca2+]i.
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Kapela A, Bezerianos A, Tsoukias NM: A mathematical model of vasoreactivity in rat mesenteric arterioles: I. Myoendothelial communication, MICROCIRC 16:8,(694-U69), 2009 Kapela A, Bezerianos A, Tsoukias NM.: A mathematical model of Ca2+ dynamics in rat mesenteric smooth muscle cell: agonist and NO stimulation, J Theor Biol 253:238-260, 2008 Silva HS, Kapela A, Tsoukias NM: A mathematical model of plasma membrane electrophysiology and calcium dynamics in vascular endothelial cells. Am J Physiol Cell Physiol 293:C277-C293, 2007
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