Open AccessSarcoplasmic reticulum Ca 2+ ‐induced Ca 2+ release regulates class II a HDAC localization in mouse embryonic cardiomyocytes
Author(s) -
Karppinen Sari,
Hänninen Sandra L.,
Rapila Risto,
Tavi Pasi
Publication year - 2018
Publication title -
physiological reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 39
ISSN - 2051-817X
DOI - 10.14814/phy2.13522
Subject(s) - endoplasmic reticulum , microbiology and biotechnology , histone deacetylase 5 , cytosol , hdac4 , myocyte , embryonic stem cell , biology , subcellular localization , chemistry , cytoplasm , histone , biochemistry , histone deacetylase , gene , enzyme
In embryonic cardiomyocytes, sarcoplasmic reticulum ( SR )‐derived Ca 2+ release is required to induce Ca 2+ oscillations for contraction and to control cardiac development through Ca 2+ ‐activated pathways. Here, our aim was to study how SR Ca 2+ release regulates cytosolic and nuclear Ca 2+ distribution and the subsequent effects on the Ca 2+ ‐dependent localization of class II a histone deacetylases ( HDAC ) and cardiac‐specific gene expression in embryonic cardiomyocytes. Confocal microscopy was used to study changes in Ca 2+ ‐distribution and localization of immunolabeled HDAC 4 and HDAC 5 upon changes in SR Ca 2+ release in mouse embryonic cardiomyocytes. Dynamics of translocation were also observed with a confocal microscope, using HDAC 5‐green fluorescent protein transfected myocytes. Expression of class II a HDAC s in differentiating myocytes and changes in cardiac‐specific gene expression were studied using real‐time quantitative PCR . Inhibition of SR Ca 2+ release caused a significant decrease in intranuclear Ca 2+ concentration, a rapid nuclear import of HDAC 5 and subnuclear redistribution of HDAC 4. Endogenous localization of HDAC 5 and HDAC 4 was mostly cytosolic and at the nuclear periphery, respectively. Downregulated expression of cardiac‐specific genes was also observed upon SR Ca 2+ release inhibition. Electrical stimulation of sarcolemmal Ca 2+ influx was not sufficient to rescue either the HDAC localization or the gene expression changes. SR Ca 2+ release controls subcellular Ca 2+ distribution and regulates localization of HDAC 4 and HDAC 5 in embryonic cardiomyocytes. Changes in SR Ca 2+ release also caused changes in expression of the developmental phase‐specific genes, which may be due to the changes in HDAC ‐localization.