Histidine-rich calcium binding protein

The new regulator of sarcoplasmic reticulum calcium cycling

Demetrios A. Arvanitis, Elizabeth Vafiadaki, Despina Sanoudou, Evangelia G. Kranias

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

The histidine-rich calcium binding protein (HRC) is a novel regulator of sarcoplasmic reticulum (SR) Ca2+-uptake, storage and release. Residing in the SR lumen, HRC binds Ca2+ with high capacity but low affinity. In vitro phosphorylation of HRC affects ryanodine affinity of the ryanodine receptor (RyR), suggesting a functional role of HRC on SR Ca2+-release. Indeed, acute HRC overexpression in isolated rodent cardiomyocytes decreases Ca2+-induced Ca2+-release, increases SR Ca2+-load, and impairs contractility. The HRC effects on RyR may be regulated by the Ca2+-sensitivity of its interaction with triadin. However, HRC also affects the SR Ca2+-ATPase, as shown by HRC overexpression in transgenic mouse hearts, which resulted in reduced SR Ca2+-uptake rates, cardiac remodeling and hypertrophy. In fact, in vitro generated evidence suggests that HRC directly interacts with SR Ca2+-ATPase2, supporting a dual role of HRC in Ca2+-homeostasis: regulation of both SR Ca2+-uptake and Ca2+-release. Furthermore, HRC plays an important role in myocyte differentiation and in antiapoptotic cardioprotection against ischemia/reperfusion induced cardiac injury. Interestingly, HRC has been linked with familiar cardiac conduction disease and an HRC polymorphism was shown to associate with malignant ventricular arrhythmias in the background of idiopathic dilated cardiomyopathy. This review summarizes studies, which have established the critical role of HRC in Ca2+-homeostasis, suggesting its importance in cardiac physiology and pathophysiology.

Original languageEnglish
Pages (from-to)43-49
Number of pages7
JournalJournal of Molecular and Cellular Cardiology
Volume50
Issue number1
DOIs
Publication statusPublished - 1 Jan 2011
Externally publishedYes

Fingerprint

Calcium-Binding Proteins
Sarcoplasmic Reticulum
Histidine
Calcium
Ryanodine Receptor Calcium Release Channel
Homeostasis
Ryanodine
Calcium-Transporting ATPases
Dilated Cardiomyopathy
Cardiomegaly
Cardiac Myocytes
Muscle Cells
Transgenic Mice
Reperfusion
Cardiac Arrhythmias
Rodentia
Heart Diseases
Ischemia
Phosphorylation
Wounds and Injuries

Keywords

  • Arrhythmia
  • Calcium-homeostasis
  • Contractility
  • Heart failure
  • HRC

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Cite this

Histidine-rich calcium binding protein : The new regulator of sarcoplasmic reticulum calcium cycling. / Arvanitis, Demetrios A.; Vafiadaki, Elizabeth; Sanoudou, Despina; Kranias, Evangelia G.

In: Journal of Molecular and Cellular Cardiology, Vol. 50, No. 1, 01.01.2011, p. 43-49.

Research output: Contribution to journalArticle

Arvanitis, Demetrios A. ; Vafiadaki, Elizabeth ; Sanoudou, Despina ; Kranias, Evangelia G. / Histidine-rich calcium binding protein : The new regulator of sarcoplasmic reticulum calcium cycling. In: Journal of Molecular and Cellular Cardiology. 2011 ; Vol. 50, No. 1. pp. 43-49.
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