A quantitative model for linking Na+/Ca2+ exchanger to SERCA during refilling of the sarcoplasmic reticulum to sustain [Ca2+] oscillations in vascular smooth muscle.
We have developed a quantitative model for the creation of cytoplasmic 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 oscillations in smooth muscle cells of the rabbit inferior vena cava. We have combined confocal microscopy data on the [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+ exchangers (NCX) on the PM to sarcoplasmic/endoplasmic reticulum 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+ to pass through the PM-SR junctions to replete the SR during the regenerative Ca2+ release, which underlies agonist induced asynchronous Ca2+ oscillations in vascular smooth muscle.
Fameli
Nicola
N
Department of Anesthesiology, Pharmacology and Therapeutics, The University of British Columbia, 2176, Health Sciences Mall, Vancouver, BC, Canada V6T 1Z3.
van Breemen
Cornelis
C
Kuo
Kuo-Hsing
KH
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003198:Computer Simulation; D066298:In Vitro Techniques; D008297:Male; D046529:Microscopy, Electron, Transmission; D008954:Models, Biological; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000648:ultrastructure; D011817:Rabbits; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism*; D019831:Sodium-Calcium Exchanger / Q000378:metabolism*
D019831:Sodium-Calcium Exchanger; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D002118:Calcium