Calcium cycling circuits in cardiac physiology and pathophysiology

K. Haghighi, D. Sanoudou, E. G. Kranias

Research output: Chapter in Book/Report/Conference proceedingChapter

2 Citations (Scopus)


Abnormal calcium cycling is a universal characteristic of human and experimental heart failure. This calcium dysregulation has been mainly attributed to the impaired function of the cardiac sarcoplasmic reticulum (SR). Abnormal Ca2+transport by the SR proteins, Ca2+ATPase (SERCA2a) and phospholamban (PLN), has been shown to have a vital role in cardiac pathophysiology and the progression of heart failure. PLN is an endogenous inhibitor of SERCA2a and as such is a primary player in cardiac relaxation by regulating Ca2+uptake. Moreover, recent studies identified other regulatory proteins in the SR Ca2+transport complex, namely inhibitor1 of protein phosphatase 1 (PP1), the small heat shock protein 20 (Hsp20), the histidinerich calcium binding protein (HRC), and the HS1 associated protein X1 (HAX1). We have shown that these new players could influence the PLN/SERCA activity and consequently, SR Ca2 +transport, cardiomyocyte Ca2 +contractility, cardiac remodeling and cell apoptosis. This article concentrates on the crucial role of the SR Ca2+handling proteins in the regulation of cardiac function and survival under physiological and pathophysiological conditions. The role of naturally occurring variants in these Ca+cycling genes, which may serve as prognostic or diagnostic factors as well as modifiers of heart failure development, is also discussed.

Original languageEnglish
Title of host publicationIntroduction to Translational Cardiovascular Research
PublisherSpringer International Publishing
Number of pages11
ISBN (Print)9783319087986, 9783319087979
Publication statusPublished - 1 Jan 2015
Externally publishedYes


  • Calcium
  • Contractility
  • Heart Failure
  • Human Variants
  • Sarcoplasmic Reticulum

ASJC Scopus subject areas

  • Medicine(all)

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    Haghighi, K., Sanoudou, D., & Kranias, E. G. (2015). Calcium cycling circuits in cardiac physiology and pathophysiology. In Introduction to Translational Cardiovascular Research (pp. 205-215). Springer International Publishing.