Modeling Ca 2+ oscillations in vascular smooth muscle cells

Abstract

Recurrent asynchronous Ca2+ waves in smooth muscle of large blood vessels involve a cycle of events starting with Ca2+ release through IP3R and concluding with refilling of the SR by coupling of reverse NCX to SERCA. We present a stochastic numerical model simulating the refilling of the SR through the junctional spaces between the plasma membrane (PM) and the sarcoplasmic reticulum (SR) of vascular smooth muscle cells. The model simulates the diffusional motion of Ca2+ through the junctional cytosol between the PM and the SR as a three-dimensional random walk from ion sources to ion sinks, representing the Na+/Ca2+ exchange carriers and SERCA pumps, respectively. The ultra-structural parameters of the junctional space are taken from serial sections of the vascular smooth muscle analyzed by electron microscopy. The boundary values for the expected Ca2+ flux through each junction per oscillation are calculated from published data relating Ca2+ movements and binding to force development. Results of the mathematical simulation corroborate the idea that Ca2+ uptake via PM-SR junctions can be sufficiently rapid and efficient to constitute a viable pathway for refilling SR calcium to maintain the Ca2+ oscillations supporting vasoconstriction induced by α-adrenergic stimulation.