Calcium Signaling and Transcriptional Regulation in Cardiomyocytes

Abstract

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.

Keywords: calcineurin; calcium; calcium-calmodulin dependent protein kinase II; calmodulin; excitation transcription coupling.