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Ca 2+ –calmodulin‐dependent protein kinase II represses cardiac transcription of the L‐type calcium channel α 1C ‐subunit gene ( Cacna1c ) by DREAM translocation
Author(s) -
Ronkainen Jarkko J.,
Hänninen Sandra L.,
Korhonen Topi,
Koivumäki Jussi T.,
Skoumal Reka,
Rautio Sini,
Ronkainen VeliPekka,
Tavi Pasi
Publication year - 2011
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2010.201400
Subject(s) - calmodulin , l type calcium channel , calcium , chemistry , microbiology and biotechnology , protein subunit , transcription factor , intracellular , calcium channel , voltage dependent calcium channel , calcium in biology , biology , biochemistry , gene , organic chemistry
Non‐technical summary In heart muscle cells, fluctuations of intracellular calcium (Ca 2+ ) concentration ([Ca 2+ ] i ) at the frequency defined by the heart rate induce contractions of the cells. Over a longer timescale the same fluctuations define the properties of the cells by regulating expressions of specific genes through the activation of a variety of cellular enzymes. In this study, we have characterized a specific cell signalling pathway, explaining how [Ca 2+ ] i regulates the expression of the L‐type calcium channel (LTCC). We show that [Ca 2+ ] i ‐activated calmodulin kinase II (CaMKII) activates downstream regulatory element (DRE) binding transcription factor DREAM, which consequently suppresses the expression of LTCCs. By experiments and mathematical modelling we demonstrate that the LTCC downregulation through the Ca 2+ –CaMKII–DREAM cascade constitutes a physiological feedback mechanism enabling cardiomyocytes to adjust the calcium intrusion through LTCCs to the amount of intracellular calcium detected by CaMKII.