Calcium sensitivity of force in human ventricular cardiomyocytes from donor and failing hearts

J. Van Der Velden, N. M. Boontje, Z. Papp, L. J. Klein, F. C. Visser, J. W. De Jong, V. J. Owen, P. B J Burton, G. J M Stienen

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

In failing human myocardium changes occur, in particular, in isoform composition and phosphorylation level of the troponin T (TnT) and troponin I (TnI) subunits of the actin filament and the myosin light chains (MLC-1 and -2), but it is unclear to what extent they influence cardiac performance. This overview concentrates on the relation between contractile function, contractile protein composition and phosphorylation levels in small biopsies from control (donor) hearts, from biopsies obtained during open heart surgery (NYHA Class I - IV) and from end-stage failing (explanted, NYHA class IV) hearts. Furthermore, attention is paid to the effect of the catalytic subunit of protein kinase A on isometric force development in single Triton-skinned human cardiomyocytes isolated from donor and end-stage failing left ventricular myocardium at different resting sarcomere lengths. A reduction in sarcomere length from 2.2 to 1.8 μm caused reductions in maximum isometric force by approximately 35% both in donor and in failing cardiomyocytes. The midpoints of the calcium sensitivity curves (pCa50) of donor and end-stage failing hearts differed markedly at all sarcomere lengths (mean ΔpCa50 = 0.22). Our findings indicate that 1) TnI phosphorylation contributes to the differences in calcium sensitivity between donor and end-stage failing hearts, 2) human ventricular myocardium is heterogeneous with respect of the phosphorylation of TnT, MLC-2 and the isoform distribution of MLC-1 and MLC-2, and 3) the Frank-Starling mechanism is preserved in end-stage failing myocardium.

Original languageEnglish
JournalBasic Research in Cardiology, Supplement
Volume97
Issue number1
Publication statusPublished - 2002

Fingerprint

Cardiac Myocytes
Sarcomeres
Myocardium
Phosphorylation
Calcium
Troponin T
Troponin I
Protein Isoforms
Cyclic AMP-Dependent Protein Kinase Catalytic Subunits
Biopsy
Starlings
Contractile Proteins
Myosin Light Chains
Actin Cytoskeleton
Thoracic Surgery

Keywords

  • Cardiomyocyte
  • Contractile protein phosphorylation
  • Frank-Starling mechanism
  • Heart failure
  • Human

ASJC Scopus subject areas

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

Cite this

Van Der Velden, J., Boontje, N. M., Papp, Z., Klein, L. J., Visser, F. C., De Jong, J. W., ... Stienen, G. J. M. (2002). Calcium sensitivity of force in human ventricular cardiomyocytes from donor and failing hearts. Basic Research in Cardiology, Supplement, 97(1).

Calcium sensitivity of force in human ventricular cardiomyocytes from donor and failing hearts. / Van Der Velden, J.; Boontje, N. M.; Papp, Z.; Klein, L. J.; Visser, F. C.; De Jong, J. W.; Owen, V. J.; Burton, P. B J; Stienen, G. J M.

In: Basic Research in Cardiology, Supplement, Vol. 97, No. 1, 2002.

Research output: Contribution to journalArticle

Van Der Velden, J, Boontje, NM, Papp, Z, Klein, LJ, Visser, FC, De Jong, JW, Owen, VJ, Burton, PBJ & Stienen, GJM 2002, 'Calcium sensitivity of force in human ventricular cardiomyocytes from donor and failing hearts', Basic Research in Cardiology, Supplement, vol. 97, no. 1.
Van Der Velden, J. ; Boontje, N. M. ; Papp, Z. ; Klein, L. J. ; Visser, F. C. ; De Jong, J. W. ; Owen, V. J. ; Burton, P. B J ; Stienen, G. J M. / Calcium sensitivity of force in human ventricular cardiomyocytes from donor and failing hearts. In: Basic Research in Cardiology, Supplement. 2002 ; Vol. 97, No. 1.
@article{8f6af3268f9f46dd81678dc113a6d51b,
title = "Calcium sensitivity of force in human ventricular cardiomyocytes from donor and failing hearts",
abstract = "In failing human myocardium changes occur, in particular, in isoform composition and phosphorylation level of the troponin T (TnT) and troponin I (TnI) subunits of the actin filament and the myosin light chains (MLC-1 and -2), but it is unclear to what extent they influence cardiac performance. This overview concentrates on the relation between contractile function, contractile protein composition and phosphorylation levels in small biopsies from control (donor) hearts, from biopsies obtained during open heart surgery (NYHA Class I - IV) and from end-stage failing (explanted, NYHA class IV) hearts. Furthermore, attention is paid to the effect of the catalytic subunit of protein kinase A on isometric force development in single Triton-skinned human cardiomyocytes isolated from donor and end-stage failing left ventricular myocardium at different resting sarcomere lengths. A reduction in sarcomere length from 2.2 to 1.8 μm caused reductions in maximum isometric force by approximately 35{\%} both in donor and in failing cardiomyocytes. The midpoints of the calcium sensitivity curves (pCa50) of donor and end-stage failing hearts differed markedly at all sarcomere lengths (mean ΔpCa50 = 0.22). Our findings indicate that 1) TnI phosphorylation contributes to the differences in calcium sensitivity between donor and end-stage failing hearts, 2) human ventricular myocardium is heterogeneous with respect of the phosphorylation of TnT, MLC-2 and the isoform distribution of MLC-1 and MLC-2, and 3) the Frank-Starling mechanism is preserved in end-stage failing myocardium.",
keywords = "Cardiomyocyte, Contractile protein phosphorylation, Frank-Starling mechanism, Heart failure, Human",
author = "{Van Der Velden}, J. and Boontje, {N. M.} and Z. Papp and Klein, {L. J.} and Visser, {F. C.} and {De Jong}, {J. W.} and Owen, {V. J.} and Burton, {P. B J} and Stienen, {G. J M}",
year = "2002",
language = "English",
volume = "97",
journal = "Basic Research in Cardiology, Supplement",
issn = "0175-9418",
publisher = "D. Steinkopff-Verlag",
number = "1",

}

TY - JOUR

T1 - Calcium sensitivity of force in human ventricular cardiomyocytes from donor and failing hearts

AU - Van Der Velden, J.

AU - Boontje, N. M.

AU - Papp, Z.

AU - Klein, L. J.

AU - Visser, F. C.

AU - De Jong, J. W.

AU - Owen, V. J.

AU - Burton, P. B J

AU - Stienen, G. J M

PY - 2002

Y1 - 2002

N2 - In failing human myocardium changes occur, in particular, in isoform composition and phosphorylation level of the troponin T (TnT) and troponin I (TnI) subunits of the actin filament and the myosin light chains (MLC-1 and -2), but it is unclear to what extent they influence cardiac performance. This overview concentrates on the relation between contractile function, contractile protein composition and phosphorylation levels in small biopsies from control (donor) hearts, from biopsies obtained during open heart surgery (NYHA Class I - IV) and from end-stage failing (explanted, NYHA class IV) hearts. Furthermore, attention is paid to the effect of the catalytic subunit of protein kinase A on isometric force development in single Triton-skinned human cardiomyocytes isolated from donor and end-stage failing left ventricular myocardium at different resting sarcomere lengths. A reduction in sarcomere length from 2.2 to 1.8 μm caused reductions in maximum isometric force by approximately 35% both in donor and in failing cardiomyocytes. The midpoints of the calcium sensitivity curves (pCa50) of donor and end-stage failing hearts differed markedly at all sarcomere lengths (mean ΔpCa50 = 0.22). Our findings indicate that 1) TnI phosphorylation contributes to the differences in calcium sensitivity between donor and end-stage failing hearts, 2) human ventricular myocardium is heterogeneous with respect of the phosphorylation of TnT, MLC-2 and the isoform distribution of MLC-1 and MLC-2, and 3) the Frank-Starling mechanism is preserved in end-stage failing myocardium.

AB - In failing human myocardium changes occur, in particular, in isoform composition and phosphorylation level of the troponin T (TnT) and troponin I (TnI) subunits of the actin filament and the myosin light chains (MLC-1 and -2), but it is unclear to what extent they influence cardiac performance. This overview concentrates on the relation between contractile function, contractile protein composition and phosphorylation levels in small biopsies from control (donor) hearts, from biopsies obtained during open heart surgery (NYHA Class I - IV) and from end-stage failing (explanted, NYHA class IV) hearts. Furthermore, attention is paid to the effect of the catalytic subunit of protein kinase A on isometric force development in single Triton-skinned human cardiomyocytes isolated from donor and end-stage failing left ventricular myocardium at different resting sarcomere lengths. A reduction in sarcomere length from 2.2 to 1.8 μm caused reductions in maximum isometric force by approximately 35% both in donor and in failing cardiomyocytes. The midpoints of the calcium sensitivity curves (pCa50) of donor and end-stage failing hearts differed markedly at all sarcomere lengths (mean ΔpCa50 = 0.22). Our findings indicate that 1) TnI phosphorylation contributes to the differences in calcium sensitivity between donor and end-stage failing hearts, 2) human ventricular myocardium is heterogeneous with respect of the phosphorylation of TnT, MLC-2 and the isoform distribution of MLC-1 and MLC-2, and 3) the Frank-Starling mechanism is preserved in end-stage failing myocardium.

KW - Cardiomyocyte

KW - Contractile protein phosphorylation

KW - Frank-Starling mechanism

KW - Heart failure

KW - Human

UR - http://www.scopus.com/inward/record.url?scp=0036285681&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036285681&partnerID=8YFLogxK

M3 - Article

C2 - 12479245

AN - SCOPUS:0036285681

VL - 97

JO - Basic Research in Cardiology, Supplement

JF - Basic Research in Cardiology, Supplement

SN - 0175-9418

IS - 1

ER -