Sarcoplasmic reticulum Ca2+ -induced Ca2+ release regulates class IIa HDAC localization in mouse embryonic cardiomyocytes
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CitationKarppinen, Sari. Hänninen, Sandra L. Rapila, Risto. Tavi, Pasi. (2018). Sarcoplasmic reticulum Ca2+ -induced Ca2+ release regulates class IIa HDAC localization in mouse embryonic cardiomyocytes. Physiological Reports, 6 (2) , e13522. 10.14814/phy2.13522.
In 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.