Titin-based modulation of calcium sensitivity of active tension in mouse skinned cardiac myocytes

Olivier Cazorla, Yiming Wu, Thomas C. Irving, Henk Granzier

Research output: Contribution to journalArticle

168 Scopus citations

Abstract

We studied the effect of titin-based passive force on the length dependence of activation of cardiac myocytes to explore whether titin may play a role in the generation of systolic force. Force-pCa relations were measured at sarcomere lengths (SLs) of 2.0 and 2.3 μm. Passive tension at 2.3 μm SL was varied from ≅1 to ≅10 mN/mm2 by adjusting the characteristics of the stretch imposed on the passive cell before activation. Relative to 2.0 μm SL, the force-pCa curve at 2.3 μm SL and low passive tension showed a leftward shift (ΔpCa50 [change in pCa at half-maximal activation]) of 0.09±0.02 pCa units while at 2.3 μm SL and high passive tension the shift was increased to 0.25±0.03 pCa units. Passive tension also increased ΔpCa50 at reduced interfilament lattice spacing achieved with dextran. We tested whether titin-based passive tension influences the interfilament lattice spacing by measuring the width of the myocyte and by using small-angle x-ray diffraction of mouse left ventricular wall muscle. Cell width and interfilament lattice spacing varied inversely with passive tension, in the presence and absence of dextran. The passive tension effect on length-dependent activation may therefore result from a radial titin-based force that modulates the interfilament lattice spacing.

Original languageEnglish (US)
Pages (from-to)1028-1035
Number of pages8
JournalCirculation research
Volume88
Issue number10
DOIs
StatePublished - May 25 2001

Keywords

  • Collagen
  • Frank-Starling
  • Myofilament lattice
  • X-ray diffraction

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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