Calcium-regulated transcriptional pathways in the normal and pathologic heart

IUBMB Life. 2011 Oct;63(10):847-55. doi: 10.1002/iub.545. Epub 2011 Sep 7.


The cytosolic calcium concentration ([Ca(2+)](c)) is key for the regulation of many cellular processes, such cell signaling and proliferation, metabolism, and muscle contraction. In cardiomyocytes, Ca(2+) is an important regulator in many cellular functions such electrophysiological processes, excitation-contraction coupling, regulation of contractile proteins activity, energy metabolism, cell death, and transcriptional regulation by the activation of Ca(2+)-dependent transcriptional pathways. In cardiomyocytes, the two main Ca(2+) -dependent pathways are the Ca(2+)/calmodulin-calcineurin-NFAT and the Ca(2+) /calmodulin-dependent kinases-MEF2. Both pathways are involved in the transcriptional control of many cardiac genes. Cardiac hypertrophy (CH) and heart failure (HF) are characterized by alterations in calcium handling such a low sarcoplasmic reticulum Ca(2+) content, decreased rate of Ca(2+) removal from the sarcoplasm, increased diastolic [Ca(2+)](c), and decreased systolic [Ca(2+)](c), all of them contributing to diminished contractibility and force generation in failing heart. At gene expression level, there are also many changes such decreased levels of SERCA2a and activation of a fetal gene expression program in cardiomyocytes. A variety of Ca(2+)-dependent signaling pathways have been implicated in CH and HF, but whether these pathways are interrelated and whether there is specificity among them are still unclear and under investigation. The focus of this review is to make an analysis of the current knowledge about the role of Ca(2+) signaling pathways in the regulation of cardiac gene expression making special emphasis in novel strategies to correct Ca(2+) handling alterations by means of SERCA2a gene therapy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Calcineurin / metabolism
  • Calcium / metabolism*
  • Calcium Signaling / physiology*
  • Calsequestrin / metabolism
  • Cardiomegaly / metabolism
  • Energy Metabolism / physiology*
  • Gene Expression Regulation / physiology*
  • Heart Failure / metabolism
  • Humans
  • MADS Domain Proteins / metabolism
  • MEF2 Transcription Factors
  • Models, Biological
  • Myocardial Contraction / physiology*
  • Myocytes, Cardiac / metabolism
  • Myocytes, Cardiac / physiology*
  • Myogenic Regulatory Factors / metabolism
  • NFATC Transcription Factors / metabolism
  • Sarcoplasmic Reticulum / metabolism
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases / metabolism


  • CASQ2 protein, human
  • Calsequestrin
  • MADS Domain Proteins
  • MEF2 Transcription Factors
  • MEF2A protein, human
  • Myogenic Regulatory Factors
  • NFATC Transcription Factors
  • Calcineurin
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases
  • Calcium