Titin-isoform dependence of titin-actin interaction and its regulation by S100A1/ Ca2+ in skinned myocardium

Hendrikus "Henk" Granzier, Hideto Fukushima, Charles S. Chung

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Titin, also known as connectin, is a large filamentous protein that greatly contributes to passive myocardial stiffness. In vitro evidence suggests that one of titin's spring elements, the PEVK, interacts with actin and that this adds a viscous component to passive stiffness. Differential splicing of titin gives rise to the stiff N2B and more compliant N2BA isoforms. Here we studied the titin-isoformdependence of titin-actin interaction and studied the bovine left atrium (BLA) that expressesmainly N2BA titin, and the bovine left ventricle (BLV) that expresses a mixture of both N2B and N2BA isforms. For comparison we also studiedmouse left ventricular (MLV) myocardium which expresses predominately N2B titin. Using the actin-severing protein gelsolin, we obtained evidence that titin-actin interaction contributes significantly to passive myocardial stiffness in all tissue types, but most in MLV, least in BLA, and an intermediate level in BLV.We also studied whether titin-actin interaction is regulated by S100A1/calcium and found that calcium alone or S100A1 alone did not alter passive stiffness, but that combined they significantly lowered stiffness.We propose that titin-actin interaction is a "viscous break" that is on during diastole and off during systole.

Original languageEnglish (US)
Article number727239
JournalJournal of Biomedicine and Biotechnology
Volume2010
DOIs
StatePublished - 2010

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Connectin
Actins
Myocardium
Protein Isoforms
Stiffness
Heart Atria
Heart Ventricles
Gelsolin
Calcium
Diastole
Systole

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Genetics
  • Molecular Biology
  • Health, Toxicology and Mutagenesis
  • Medicine(all)

Cite this

Titin-isoform dependence of titin-actin interaction and its regulation by S100A1/ Ca2+ in skinned myocardium. / Granzier, Hendrikus "Henk"; Fukushima, Hideto; Chung, Charles S.

In: Journal of Biomedicine and Biotechnology, Vol. 2010, 727239, 2010.

Research output: Contribution to journalArticle

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