Sorcin regulates excitation-contraction coupling in the heart

Marian B. Meyers, Avi Fischer, Yan Jie Sun, Coeli M.B. Lopes, Tibor Rohacs, Tomoe Y. Nakamurall, Ying Ying Zhoull, Paul C. Lee, Ruth A. Altschuld, Sylvia A. McCune, William A. Coetzeell, Glenn I. Fishman

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

Sorcin is a penta-EF hand Ca2+-binding protein that associates with both cardiac ryanodine receptors and L-type Ca2+ channels and has been implicated in the regulation of intracellular Ca2+ cycling. To better define the function of sorcin, we characterized transgenic mice in which sorcin was overexpressed in the heart. Transgenic mice developed normally with no evidence of cardiac hypertrophy and no change in expression of other calcium regulatory proteins. In vivo hemodynamics revealed significant reductions in global indices of contraction and relaxation. Contractile abnormalities were also observed in isolated adult transgenic myocytes, along with significant depression of Ca2+ transient amplitudes. Whole cell ICa density and the time course of activation were normal in transgenic myocytes, but the rate of inactivation was significantly accelerated. These effects of sorcin on L-type Ca2+ currents were confirmed in Xenopus oocyte expression studies. Finally, we examined the expression of sorcin in normal and failing hearts from spontaneous hypertensive heart failure rats. In normal myocardium, sorcin extensively co-localized with ryanodine receptors at the Z-lines, whereas in myopathic hearts the degree of co-localization was markedly disrupted. Together, these data indicate that sorcin modulates intracellular Ca2+ cycling and Ca2+ influx pathways in the heart.

Original languageEnglish (US)
Pages (from-to)28865-28871
Number of pages7
JournalJournal of Biological Chemistry
Volume278
Issue number31
DOIs
StatePublished - Aug 1 2003
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'Sorcin regulates excitation-contraction coupling in the heart'. Together they form a unique fingerprint.

Cite this