Titin isoform-dependent effect of calcium on passive myocardial tension

Hideaki Fujita, Dietmar Labeit, Brenda Gerull, Siegfried Labeit, Henk L. Granzier

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

We studied the effects of Ca2+ on titin (connectin)-based passive tension in skinned myocardium expressing either predominantly N2B titin (rat right ventricle, RRV) or predominantly N2BA titin (bovine left atrium, BLA). Actomyosin-based tension was abolished to undetectably low levels by selectively removing the thin filaments with a Ca2+-insensitive gelsolin fragment (FX-45). Myocardium was stretched in the presence and absence of Ca2+, and passive tension was measured. Ca2+ significantly increased passive tension during and after stretch in the BLA. The increase was insensitive to the actomyosin inhibitor 2,3-butanedione 2-monoxime, supporting the conclusion that the effect is titin based. Passive tension did not respond to calcium in the RRV, indicating that passive tension developed by N2B titin is calcium insensitive. Western blot analysis and immunofluorescence studies indicated that N2BA titin expresses E-rich PEVK motifs, whereas they are absent from N2B titin, supporting earlier single molecule studies that reported that E-rich motifs are required for calcium sensitivity. We conclude that calcium affects passive myocardial tension in a titin isoform-dependent manner.

Original languageEnglish (US)
Pages (from-to)H2528-H2534
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume287
Issue number6 56-6
DOIs
StatePublished - Dec 2004

Keywords

  • Connectin
  • Diastole
  • Passive stiffness
  • Proline-glutamate-valine-lysine residue

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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