A quantitative model for linking Na+/Ca2+Na+/Ca2+ exchanger to SERCA during refilling of the sarcoplasmic reticulum to sustain [Ca2+][Ca2+] oscillations in vascular smooth muscle

We have developed a quantitative model for the creation of cytoplasmic Ca2+Ca2+ gradients near the inner surface of the plasma membrane (PM). In particular we simulated the refilling of the sarcoplasmic reticulum (SR) via PM–SR junctions during asynchronous [Ca2+]i[Ca2+]i oscillations in smooth muscle cells of the rabbit inferior vena cava  . We have combined confocal microscopy data on the [Ca2+]i[Ca2+]i oscillations, force transduction data from cell contraction studies and electron microscopic images to build a basis for computational simulations that model the transport of calcium ions from Na+/Ca2+Na+/Ca2+ exchangers (NCX) on the PM to sarcoplasmic/endoplasmic reticulum Ca2+Ca2+ ATPase (SERCA) pumps on the SR as a three-dimensional random walk through the PM–SR junctional cytoplasmic spaces. Electron microscopic ultrastructural images of the smooth muscle cells were elaborated with software algorithms to produce a very clear and dimensionally accurate picture of the PM–SR junctions. From this study, we conclude that it is plausible and possible for enough Ca2+Ca2+ to pass through the PM–SR junctions to replete the SR during the regenerative Ca2+Ca2+ release, which underlies agonist induced asynchronous Ca2+Ca2+ oscillations in vascular smooth muscle.