Importance of Altered Levels of SERCA, IP₃R, and RyR in Vascular Smooth Muscle Cell

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• 作者：Jaijus Pallippadan Johny¹ ; Michael J. Plank² ; Tim David¹ ; ^{tim.david@canterbury.ac.nz}
• 刊名：Biophysical Journal
• 出版年：2017
• 出版时间：24 January 2017
• 年：2017
• 卷：112
• 期：2
• 页码：265-287
• 全文大小：1987 K
• 卷排序：112

文摘

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.