title: Importance of Altered Levels of SERCA, IP3R, and RyR in Vascular Smooth Muscle Cell.
abstract: Calcium cycling between the sarcoplasmic reticulum (SR) and the cytosol via the sarco-/endoplasmic reticulum Ca-ATPase (SERCA) pump, inositol-1,4,5-triphosphate receptor (IP3R), and Ryanodine receptor (RyR), plays a major role in agonist-induced intracellular calcium ([Ca2+]cyt) dynamics in vascular smooth muscle cells (VSMC). Levels of these calcium handling proteins in SR get altered under disease conditions. We have developed a mathematical model to understand the significance of altered levels of SERCA, IP3R, and RyR on the intracellular calcium dynamics of VSMC and to understand how variation in protein levels that arise due to diabetes contribute to different VSMC behavior and thus vascular disease. SR is modeled as a single continuous entity with homogeneous intra-SR calcium. Model results show that agonist-induced intracellular calcium dynamics can be modified by changing the levels of SERCA, IP3R, and/or RyR. Lowering SERCA level will enable intracellular calcium oscillations at low agonist concentrations whereas lowered levels of IP3R and RyR need higher agonist concentration for intracellular calcium oscillations. This research suggests that reduced SERCA level is the main factor responsible for the reduced intracellular calcium transients and contractility in VSMCs.
authors.affiliation: Department of Mechanical Engineering, University of Canterbury, Christchurch, Canterbury, New Zealand.
authors.forename: Jaijus Pallippadan
authors.initials: JP
authors.lastname: Johny
authors.affiliation: Department of Mathematics and Statistics, University of Canterbury, Christchurch, Canterbury, New Zealand.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Plank
authors.affiliation: Department of Mechanical Engineering, University of Canterbury, Christchurch, Canterbury, New Zealand. Electronic address: tim.david@canterbury.ac.nz.
authors.forename: Tim
authors.initials: T
authors.lastname: David
mesh_terms: D002118:Calcium / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism*; D008954:Models, Biological; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism*
chemical_list: D053496:Inositol 1,4,5-Trisphosphate Receptors; D019837:Ryanodine Receptor Calcium Release Channel; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D002118:Calcium