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3 results on '"cardiac ryanodine receptors"'

1. Roles of β-adrenoceptor Subtypes and Therapeutics in Human Cardiovascular Disease: Heart Failure, Tachyarrhythmias and Other Cardiovascular Disorders

Author

Wong, Yee Weng, Haqqani, Haris, Molenaar, Peter, Michel, Martin C., Editor-in-Chief, Barrett, James E., Editorial Board Member, Centurión, David, Editorial Board Member, Flockerzi, Veit, Editorial Board Member, Geppetti, Pierangelo, Editorial Board Member, Hofmann, Franz B., Editorial Board Member, Meier, Kathryn Elaine, Editorial Board Member, Page, Clive P., Editorial Board Member, Seifert, Roland, Editorial Board Member, Wang, KeWei, Editorial Board Member, Baker, Jillian G., editor, and Summers, Roger J., editor

Published
2024
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2. Age-related regulation of excitation-contraction coupling in rat heart.

Author

Kandilci, Hilmi, Tuncay, Erkan, Zeydanli, Esma, Sozmen, Nazli, and Turan, Belma

Abstract

Hearts from subjects with different ages have different Ca signaling. Release of Ca from intracellular stores in response to an action potential initiates cardiac contraction. Both depolarization-stimulated and spontaneous Ca releases, Ca transients and Ca sparks, demonstrate the main events of excitation-contraction coupling (ECC). Global increase in free Ca concentration ([Ca]) consists of summation of Ca release events in cardiomyocytes. Since the Ca flux induced by Ca sparks reports a summation of ryanodine-sensitive Ca release channels (RyR2s)'s behavior in a spark cluster, evaluation of the properties of Ca sparks and Ca transients may provide insight into the role of RyR2s on altered heart function between 3-month-old (young adult) and 6-month-old (mature adult) rats. Basal [Ca] and Ca sparks frequency were significantly higher in mature adult rats compared to those of young adults. Moreover, amplitudes of Ca sparks and Ca transients were significantly smaller in mature adults than those of young adults with longer time courses. A smaller L-type Ca current density and decreased SR Ca load was observed in mature adult rats. In addition, RyR2s were markedly hyperphosphorylated, and phosphorylation levels of PKA and CaMKII were higher in heart from mature adults compared to those of young adults, whereas their SERCA protein levels were similar. Our data demonstrate that hearts from rats with different ages have different Ca signaling including hyperphosphorylation of RyR2s and higher basal [Ca] together with increased oxidized protein-thiols in mature adult rats compared to those of young adults, which play important roles in ECC. Finally, we report that ECC efficiency changes with age during maturation, partially related with an increased cellular oxidation level leading to reduced free protein-thiols in cardiomyocytes. [ABSTRACT FROM AUTHOR]

Published
2011
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3. Carbonylation Induces Heterogeneity in Cardiac Ryanodine Receptors (RyR2) Function During Diabetes

Author

Shao, Chunhong, Tian, Chengju, Ouyang, Shouqiang, Moore, Caronda, Alomar, Fadhel, Nemet, Ina, D'Souza, Alicia, Nagai, Ryoji, Kutty, Shelby, Rozanski, George J., Ramanadham, Sasanka, Singh, Jaipaul, and Bidasee, Keshore

Subjects
heart failure, arrhythmias, cardiac ryanodine receptors, diabetes, carbonylation, methylglyoxal, cardiovascular system
Abstract

Heart failure and arrhythmias occur at rates 3-5 times higher in individuals with diabetes mellitus compared with age-matched, healthy individuals. Studies attribute these defects in part to alterations in function of cardiac ryanodine receptors (RyR2), the principal Ca2+ release channel on the internal sarcoplasmic reticulum (SR). To date, mechanisms underlying RyR2 dysregulation during diabetes remain poorly defined. A rat model of type 1 diabetes, in combination with echocardiography, in vivo and ex vivo hemodynamics, video edge-detection, confocal microscopy, Western blots, mass spectrometry, site-directed mutagenesis, [3H]ryanodine binding, lipid bilayer and transfection assays were used to ascertain if post-translational modifications by reactive carbonyl species (RCS) are a contributing cause. After 8 weeks of diabetes, spontaneous Ca2+ release in ventricular myocytes increased ~5-fold. Evoked Ca2+ release from the SR was also non-uniformed (dyssynchronous). Total RyR2 protein remained unchanged, but its ability to bind the Ca2+-dependent ligand [3H]ryanodine was significantly reduced. Western blots and mass spectrometry revealed RCS adducts on select basic residues. Mutating residues to delineate the physiochemical impact of carbonylation yielded channels with enhanced and reduced cytoplasmic Ca2+-responsiveness. The prototype RCS methylglyoxal (MGO) increased then decreased the open probability (Po) of RyR2. MGO also increased spontaneous Ca2+ release and induced Ca2+ waves in healthy myocytes. Treating diabetic rats with RCS scavengers normalized spontaneous and evoked Ca2+ release from the SR, reduced carbonylation of RyR2, and increased binding of [3H]ryanodine to RyR2. From these data we conclude that posttranslational modification by RCS is a contributing cause for heterogeneity in RyR2 activity seen during experimental diabetes.

Published
2012

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