Dataset Information

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.

SUBMITTER: Johny JP

PROVIDER: S-EPMC5266201 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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

Johny Jaijus Pallippadan JP Plank Michael J MJ David Tim T

Biophysical journal 20170101 2

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 ...[more]

PMID: 28122214

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Project description:Mitochondria are widely described as being highly dynamic and adaptable organelles, and their movement is thought to be vital for cell function. Yet, in various native cells, including those of heart and smooth muscle, mitochondria are stationary and rigidly structured. The significance of the differences in mitochondrial behavior to the physiological function of cells is unclear and was studied in single myocytes and intact resistance-sized cerebral arteries. We hypothesized that mitochondrial dynamics is controlled by the proliferative status of the cells.High-speed fluorescence imaging of mitochondria in live vascular smooth muscle cells shows that the organelle undergoes significant reorganization as cells become proliferative. In nonproliferative cells, mitochondria are individual (? 2 ?m by 0.5 ?m), stationary, randomly dispersed, fixed structures. However, on entering the proliferative state, mitochondria take on a more diverse architecture and become small spheres, short rod-shaped structures, long filamentous entities, and networks. When cells proliferate, mitochondria also continuously move and change shape. In the intact pressurized resistance artery, mitochondria are largely immobile structures, except in a small number of cells in which motility occurred. When proliferation of smooth muscle was encouraged in the intact resistance artery, in organ culture, the majority of mitochondria became motile and the majority of smooth muscle cells contained moving mitochondria. Significantly, restriction of mitochondrial motility using the fission blocker mitochondrial division inhibitor prevented vascular smooth muscle proliferation in both single cells and the intact resistance artery.These results show that mitochondria are adaptable and exist in intact tissue as both stationary and highly dynamic entities. This mitochondrial plasticity is an essential mechanism for the development of smooth muscle proliferation and therefore presents a novel therapeutic target against vascular disease.

Dataset Information

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

Publications

Importance of Altered Levels of SERCA, IP<sub>3</sub>R, and RyR in Vascular Smooth Muscle Cell.

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