Aim: 

Spontaneous activity of the developing embryonic cardiomyocytes originates from the calcium oscillations triggered by sarcoplasmic reticulum (SR) calcium release. These oscillations maintain the heart beat and are also essential in development of the cardiac muscle. In order to find the links between cell activity and gene expression in embryonic cardiomyocytes, we studied the cellular translocation of class IIa histone deacetylases (HDACs), which are known to control the activity -dependent gene expression in variety of cell types.

Methods: 

Isolated mouse embryonic cardiomyocytes (E10) were used for intracellular calcium measurements with Fluo4-AM and antibody-labelling of HDAC5. HDAC5 translocation was measured with a confocal microscope in HDAC5-GFP transfected cardiomyocytes.

Results: 

HDAC5 was found to be localised mainly in the cytosol in spontaneously active cells. However, inhibition of the SR calcium with ryanodine caused the translocation of endogenous and HDAC5-GFP into the nucleus with t[asymp] 20 minutes. Electrical stimulation-induced calcium influx through L-type calcium channels alone was not sufficient to prevent the nuclear import of HDAC5 induced by ryanodine. Calcium/calmodulin-dependent protein kinase II (CaMKII) has been shown to regulate HDAC-activity in cardiomyocytes. Inhibition of CaMKII by KN-93 had no effect on the cytosol -localised HDAC5. However, when ryanodine was used to translocate HDAC5 into the nucleus, CaMKII-inhibition caused its subsequent nuclear export with t[asymp] 14 minutes.

Conclusion: 

Spontaneous activity of the early embryonic cardiomyocytes regulates nuclear-cytoplasmic shuttling of HDAC5, establishing a link between cell activity and gene expression in embryonic cardiomyocytes. SR calcium release is indispensable for removal of HDAC-dependent repression of embryonic gene expression.