Sarcoplasmic reticulum Ca²⁺‐induced Ca²⁺ release regulates class IIa HDAC localization in mouse embryonic cardiomyocytes

Publisher： John Wiley & Sons Inc

E-ISSN： 2051-817x|6|2|phy2.13522-phy2.13522

ISSN： 2051-817X

Source： Physiological Reports, Vol.6, Iss.2, 2018-01, pp. : n/a-n/a

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Abstract

AbstractIn embryonic cardiomyocytes, sarcoplasmic reticulum (SR)‐derived Ca²⁺ release is required to induce Ca²⁺ oscillations for contraction and to control cardiac development through Ca²⁺‐activated pathways. Here, our aim was to study how SR Ca²⁺ release regulates cytosolic and nuclear Ca²⁺ distribution and the subsequent effects on the Ca²⁺‐dependent localization of class IIa histone deacetylases (HDAC) and cardiac‐specific gene expression in embryonic cardiomyocytes. Confocal microscopy was used to study changes in Ca²⁺‐distribution and localization of immunolabeled HDAC4 and HDAC5 upon changes in SR Ca²⁺ release in mouse embryonic cardiomyocytes. Dynamics of translocation were also observed with a confocal microscope, using HDAC5‐green fluorescent protein transfected myocytes. Expression of class IIa HDACs in differentiating myocytes and changes in cardiac‐specific gene expression were studied using real‐time quantitative PCR. Inhibition of SR Ca²⁺ release caused a significant decrease in intranuclear Ca²⁺ concentration, a rapid nuclear import of HDAC5 and subnuclear redistribution of HDAC4. Endogenous localization of HDAC5 and HDAC4 was mostly cytosolic and at the nuclear periphery, respectively. Downregulated expression of cardiac‐specific genes was also observed upon SR Ca²⁺ release inhibition. Electrical stimulation of sarcolemmal Ca²⁺ influx was not sufficient to rescue either the HDAC localization or the gene expression changes. SR Ca²⁺ release controls subcellular Ca²⁺ distribution and regulates localization of HDAC4 and HDAC5 in embryonic cardiomyocytes. Changes in SR Ca²⁺ release also caused changes in expression of the developmental phase‐specific genes, which may be due to the changes in HDAC‐localization.