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Depressed Sarcoplasmic Reticulum Activity Underlies Ca 2+ Dyshomeostasis in A Rat Model of Metabolic Syndrome
Author(s) -
OKATAN ESMA,
TUNCAY ERKAN,
TURAN Belma
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.951.6
Subject(s) - serca , phospholamban , medicine , endocrinology , ryanodine receptor 2 , ryanodine receptor , endoplasmic reticulum , myocyte , chemistry , caffeine , calsequestrin , calcium , atpase , biochemistry , enzyme
High‐carbohydrate diet‐induced obesity and/or metabolic syndrom (MetS) is recognized as an independent risk factor for dysfunctioning of the heart. Although several mechanisms have been postulated for its identification, no precise mechanism is available yet for the cardiac remodeling and contractile dysfunction under MetS. Therefore, we aimed to investigate the role of sarcoplasmic reticulum (SR) on altered intracellular Ca 2+ regulation in cardiomyocytes from MetS male rats, induced with high‐sucrose drinking water during 16‐week period. Basically, electrically‐stimulated Ca 2 + transients and L‐type Ca 2+ ‐currents (LTCC) were recorded in ventricular myocytes from MetS rats relative to myocytes from control rats. We also investigated SR‐Ca 2+ ‐ATPase (SERCA) activity as well as phosphorylation levels of cardiac ryanodine receptor (RyR2) family proteins by Western blot analysis. The Ca 2+ transients exhibited significantly reduced amplitude (~30%), and prolonged time courses (2‐fold) with no change in LTCC as well as depressed Ca 2+ loading of SR (~55%) due to caffeine responses in cardiomyoctes from MetS rats with increased basal Ca 2+ compared to aged‐matched control rats. Our data with caffeine responses under 0Na0Ca also demonstrated a depressed SERCA activity in MetS cardiomyocytes which supported further the data on a slowed cytosolic Ca 2+ removal associated with a significant decrease in SERCA2‐mediated Ca 2+ reuptake. Additionally, the data with tetracaine application assay was supporting a leaky‐RyR2 in cardiomyocytes from MetS group. Moreover, high phosphorylation levels of both RyR2 and phospholamban are supporting a depressed SR activity which underlies Ca 2+ dyshomeostasis in MetS rat model. (Supported by TUBITAK‐SBAG‐111S042)