Role of electrical current and diffusion of second messengers in Ca 2+ synchronization during vasomotion in microcirculation: Theoretical models

Synchronization of calcium (Ca 2+ ) oscillations in vascular smooth muscle cells (SMCs) is a prerequisite for the phenomenon of vasomotion occurring in many vascular beds. The mechanisms of synchronization remain unclear and may depend on spatial Ca 2+ and/or IP3 gradients and local arrangement of subcellular components. To improve the fundamental understanding of intra‐ and intercellular signaling pathways involved during vasomotion, we used detail models of Ca 2+ and membrane potential dynamics in isolated SMC and EC to formulate a multi‐cellular model of vessel wall. A 2‐dimensional model of SMCs using finite element methods was also developed to study the spatial gradients of IP3 and Ca 2+ waves within SMCs. The results indicate that under certain conditions Ca 2+ oscillations in smooth muscle cells can be synchronized through electrical currents generated by Ca 2+ dependent chloride channels and DAG activated NSC channels and spreading through gap junctions. Intercellular diffusion of oscillatory IP3 can also contribute to synchronization. The model allows for spatial visualization of signaling events inside cells and examining the effects of localization of IP3 and ryanodine receptors on synchronization. The study provides a novel theoretical tool to examine the mechanisms of synchronization in vascular vasomotion.(Supported by NIH SC1HL95101).