Journal
CIRCULATION RESEARCH
Volume 121, Issue 8, Pages 1000-1020Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCRESAHA.117.310355
Keywords
calcium; calcium-calmodulin dependent protein kinase II; calcineurin; calmodulin; excitation transcription coupling
Funding
- DZHK (Deutsches Zentrum fur Herz-Kreislauf-Forschung-German Centre for Cardiovascular Research)
- BMBF (German Ministry of Education and Research)
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Calcium (Ca2+) is a universal regulator of various cellular functions. In cardiomyocytes, Ca2+ is the central element of excitation-contraction coupling, but also impacts diverse signaling cascades and influences the regulation of gene expression, referred to as excitation-transcription coupling. Disturbances in cellular Ca2+-handling and alterations in Ca2+-dependent gene expression patterns are pivotal characteristics of failing cardiomyocytes, with several excitation-transcription coupling pathways shown to be critically involved in structural and functional remodeling processes. Thus, targeting Ca2+-dependent transcriptional pathways might offer broad therapeutic potential. In this article, we (1) review cytosolic and nuclear Ca2+ dynamics in cardiomyocytes with respect to their impact on Ca2+-dependent signaling, (2) give an overview on Ca2+-dependent transcriptional pathways in cardiomyocytes, and (3) discuss implications of excitation-transcription coupling in the diseased heart.
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