Differential effects of S100 proteins A2 and A6 on cardiac Ca2+ cycling and contractile performance

Wang Wang, Michelle L. Asp, Guadalupe Guerrero-Serna, Joseph M. Metzger

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Defective intracellular calcium (Ca2+) handling is implicated in the pathogenesis of heart failure. Novel approaches targeting both cardiac Ca2+ release and reuptake processes, such as S100A1, have the potential to rescue the function of failing cardiac myocytes. Here, we show that two members of the S100 Ca2+ binding protein family, S100A2 and S100A6 that share high sequence homology, differentially influence cardiac Ca2+ handling and contractility. Cardiac gene expression of S100A2 significantly enhanced both contractile and relaxation performance of rodent and canine cardiac myocytes, mimicking the functional effects of its cardiac homologue, S100A1. To interrogate mechanism, Ca2+ spark frequency, a measure of the gating of the ryanodine receptor Ca2+ release channel, was found to be significantly increased by S100A2. Therapeutic testing showed that S100A2 rescued the contractile defects of failing cardiac myocytes. In contrast, cardiac expression of S100A6 had no significant effects on contractility or Ca2+ handling. These data reveal novel differential effects of S100 proteins on cardiac myocyte performance that may be useful in application to diseased cardiac muscle.

Original languageEnglish (US)
Pages (from-to)117-125
Number of pages9
JournalJournal of Molecular and Cellular Cardiology
Volume72
DOIs
StatePublished - Jul 2014

Bibliographical note

Funding Information:
We thank Rick Turner, Kim Converso and Lakshmi Mundada for technical assistance. We thank the Lillehei Heart Institute for support. This work was supported by grants from the NIH to WW ( HL114760 ) and JMM ( HL059301 and AG034107 ).

Keywords

  • Cardiac calcium handling
  • Excitation-contraction coupling
  • Gene therapy
  • Heart failure
  • S100 proteins

Fingerprint

Dive into the research topics of 'Differential effects of S100 proteins A2 and A6 on cardiac Ca<sup>2+</sup> cycling and contractile performance'. Together they form a unique fingerprint.

Cite this