کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5530587 1549314 2017 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Increased calcium leak associated with reduced calsequestrin expression in hyperthyroid cardiomyocytes
ترجمه فارسی عنوان
افزایش نشت کلسیم همراه با کاهش بیان کالس تسترین در کراتومیوسیت های هیپوتیروئید
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
چکیده انگلیسی


- Abnormal calcium leak and arrhythmogenic activity is observed in cardiomyocytes of hyperthyroid rats.
- Abnormal cardiomyocyte calcium leak in hyperthyroidism is related to a reduction in calsequestrin-2 expression rather than SR Ca2+ overload.
- The reduction in calsequestrin-2 expression along with increased SERCA pump activity promoted a gain-of-function in RyRs without changes in SR Ca2+ load.

IntroductionCalcium (Ca2+) leak during cardiac diastole is chiefly mediated by intracellular Ca2+ channel/Ryanodine Receptors. Increased diastolic Ca2+ leak has been proposed as the mechanism underlying the appearance of hereditary arrhythmias. However, little is known about alterations in diastolic Ca2+ leak and the specific roles played by key intracellular Ca2+-handling proteins in hyperthyroidism, a known arrhythmogenic condition.AimWe sought to determine whether there were modifications in diastolic Ca2+ leak, based on the recording of Ca2+ sparks and Ca2+ waves; we also investigated changes in the expression and activity of key Ca2+ handling proteins, including ryanodine receptors, Sarco-Endoplasmic Reticulum Ca2+ ATPase pump and calsequestrin in isolated left-ventricular cardiomyocytes isolated from hyperthyroid rats.Materials and methodsElectrocardiography (ECG) recordings were performed in control and hyperthyroid rats. Ca2+ sparks, Ca2+ waves, and electrically-stimulated Ca2+ transients were recorded in Fluo-3-loaded cardiomyocytes from both experimental groups using confocal microscopy. In addition, left-ventricular homogenates and Ryanodine Receptor-enriched membrane fractions were prepared for assessing [3H]-ryanodine binding, hydrolytic ATPase activity of SERCA pump and expression levels of key proteins by Western blot, and cDNA for real-time qPCR.Results and conclusionsExtrasystoles were observed in hearts of hyperthyroid rats by ECG recordings. Arrhythmogenic activity, high incidence of Ca2+ waves, and de novo Ca2+ wavelets −in the absence of sarcoplasmic reticulum Ca2+ overload- were recorded in these cardiomyocytes. The exacerbated diastolic Ca2+ leak and arrhythmogenic activities were related to a diminished expression of calsequestrin along with increased SERCA pump activity, which, in effect, promoted a gain-of-function in RyRs without alterations in SR Ca2+ load, RyR expression or its Ca2+ sensitivity.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cell Calcium - Volume 62, March 2017, Pages 29-40
نویسندگان
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