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

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

Research output: Contribution to journalArticle

165 Citations (Scopus)

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
StatePublished - May 25 2001
Externally publishedYes

Fingerprint

Connectin
Sarcomeres
Cardiac Myocytes
Calcium
Dextrans
Muscle Cells
X-Rays
Muscles

Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Titin-based modulation of calcium sensitivity of active tension in mouse skinned cardiac myocytes. / Cazorla, Olivier; Wu, Yiming; Irving, Thomas C.; Granzier, Hendrikus "Henk".

In: Circulation Research, Vol. 88, No. 10, 25.05.2001, p. 1028-1035.

Research output: Contribution to journalArticle

Cazorla, Olivier ; Wu, Yiming ; Irving, Thomas C. ; Granzier, Hendrikus "Henk". / Titin-based modulation of calcium sensitivity of active tension in mouse skinned cardiac myocytes. In: Circulation Research. 2001 ; Vol. 88, No. 10. pp. 1028-1035.
@article{d758f5345ac64bbd82bfa1e6a12f59ec,
title = "Titin-based modulation of calcium sensitivity of active tension in mouse skinned cardiac myocytes",
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.",
keywords = "Collagen, Frank-Starling, Myofilament lattice, X-ray diffraction",
author = "Olivier Cazorla and Yiming Wu and Irving, {Thomas C.} and Granzier, {Hendrikus {"}Henk{"}}",
year = "2001",
month = "5",
day = "25",
language = "English (US)",
volume = "88",
pages = "1028--1035",
journal = "Circulation Research",
issn = "0009-7330",
publisher = "Lippincott Williams and Wilkins",
number = "10",

}

TY - JOUR

T1 - Titin-based modulation of calcium sensitivity of active tension in mouse skinned cardiac myocytes

AU - Cazorla, Olivier

AU - Wu, Yiming

AU - Irving, Thomas C.

AU - Granzier, Hendrikus "Henk"

PY - 2001/5/25

Y1 - 2001/5/25

N2 - 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.

AB - 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.

KW - Collagen

KW - Frank-Starling

KW - Myofilament lattice

KW - X-ray diffraction

UR - http://www.scopus.com/inward/record.url?scp=0035947754&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035947754&partnerID=8YFLogxK

M3 - Article

VL - 88

SP - 1028

EP - 1035

JO - Circulation Research

JF - Circulation Research

SN - 0009-7330

IS - 10

ER -