Effects of calcium, inorganic phosphate, and pH on isometric force in single skinned cardiomyocytes from donor and failing human hearts

J. Van Der Velden, L. J. Klein, R. Zaremba, N. M. Boontje, M. A.J.M. Huybregts, W. Stooker, L. Eijsman, J. W. De Jong, C. A. Visser, F. C. Visser, G. J.M. Stienen

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background - During ischemia, the intracellular calcium and inorganic phosphate (Pi) concentrations rise and pH falls. We investigated the effects of these changes on force development in donor and failing human hearts to determine if altered contractile protein composition during heart failure changes the myocardial response to Ca2+, Pi, and pH. Methods and Results - Isometric force was studied in mechanically isolated Triton-skinned single myocytes from left ventricular myocardium. Force declined with added Pi to 0.33±0.02 of the control force (pH 7.1, 0 mmol/L Pi) at 30 mmol/L Pi and increased with pH from 0.64±0.03 at pH 6.2 to 1.27±0.02 at pH 7.4. Force dependency on Pi and pH did not differ between donor and failing hearts. Incubation of myocytes in a Pi-containing activating solution caused a potentiation of force, which was larger at submaximal than at maximal [Ca2+]. Ca2+ sensitivity of force was similar in donor hearts and hearts with moderate cardiac disease, but in end-stage failing myocardium it was significantly increased. The degree of myosin light chain 2 phosphorylation was significantly decreased in end-stage failing compared with donor myocardium, resulting in an inverse correlation between Ca2+ responsiveness of force and myosin light chain 2 phosphorylation. Conclusions - Our results indicate that contractile protein alterations in human end-stage heart failure alter Ca2+ responsiveness of force but do not affect the force-generating capacity of the cross-bridges or its Pi and pH dependence. In end-stage failing myocardium, the reduction in force by changes in pH and [Pi] at submaximal [Ca2+] may even be less than in donor hearts because of the increased Ca2+ responsiveness.

Original languageEnglish
Pages (from-to)1140-1146
Number of pages7
JournalCirculation
Volume104
Issue number10
DOIs
Publication statusPublished - 4 Sep 2001

Cite this

Van Der Velden, J., Klein, L. J., Zaremba, R., Boontje, N. M., Huybregts, M. A. J. M., Stooker, W., ... Stienen, G. J. M. (2001). Effects of calcium, inorganic phosphate, and pH on isometric force in single skinned cardiomyocytes from donor and failing human hearts. Circulation, 104(10), 1140-1146. https://doi.org/10.1161/hc3501.095485
Van Der Velden, J. ; Klein, L. J. ; Zaremba, R. ; Boontje, N. M. ; Huybregts, M. A.J.M. ; Stooker, W. ; Eijsman, L. ; De Jong, J. W. ; Visser, C. A. ; Visser, F. C. ; Stienen, G. J.M. / Effects of calcium, inorganic phosphate, and pH on isometric force in single skinned cardiomyocytes from donor and failing human hearts. In: Circulation. 2001 ; Vol. 104, No. 10. pp. 1140-1146.
@article{8cd1cd10fe324315946cef1cfbff975e,
title = "Effects of calcium, inorganic phosphate, and pH on isometric force in single skinned cardiomyocytes from donor and failing human hearts",
abstract = "Background - During ischemia, the intracellular calcium and inorganic phosphate (Pi) concentrations rise and pH falls. We investigated the effects of these changes on force development in donor and failing human hearts to determine if altered contractile protein composition during heart failure changes the myocardial response to Ca2+, Pi, and pH. Methods and Results - Isometric force was studied in mechanically isolated Triton-skinned single myocytes from left ventricular myocardium. Force declined with added Pi to 0.33±0.02 of the control force (pH 7.1, 0 mmol/L Pi) at 30 mmol/L Pi and increased with pH from 0.64±0.03 at pH 6.2 to 1.27±0.02 at pH 7.4. Force dependency on Pi and pH did not differ between donor and failing hearts. Incubation of myocytes in a Pi-containing activating solution caused a potentiation of force, which was larger at submaximal than at maximal [Ca2+]. Ca2+ sensitivity of force was similar in donor hearts and hearts with moderate cardiac disease, but in end-stage failing myocardium it was significantly increased. The degree of myosin light chain 2 phosphorylation was significantly decreased in end-stage failing compared with donor myocardium, resulting in an inverse correlation between Ca2+ responsiveness of force and myosin light chain 2 phosphorylation. Conclusions - Our results indicate that contractile protein alterations in human end-stage heart failure alter Ca2+ responsiveness of force but do not affect the force-generating capacity of the cross-bridges or its Pi and pH dependence. In end-stage failing myocardium, the reduction in force by changes in pH and [Pi] at submaximal [Ca2+] may even be less than in donor hearts because of the increased Ca2+ responsiveness.",
keywords = "Contractility, Heart failure, Ischemia, Myocytes, Proteins",
author = "{Van Der Velden}, J. and Klein, {L. J.} and R. Zaremba and Boontje, {N. M.} and Huybregts, {M. A.J.M.} and W. Stooker and L. Eijsman and {De Jong}, {J. W.} and Visser, {C. A.} and Visser, {F. C.} and Stienen, {G. J.M.}",
year = "2001",
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language = "English",
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Van Der Velden, J, Klein, LJ, Zaremba, R, Boontje, NM, Huybregts, MAJM, Stooker, W, Eijsman, L, De Jong, JW, Visser, CA, Visser, FC & Stienen, GJM 2001, 'Effects of calcium, inorganic phosphate, and pH on isometric force in single skinned cardiomyocytes from donor and failing human hearts' Circulation, vol. 104, no. 10, pp. 1140-1146. https://doi.org/10.1161/hc3501.095485

Effects of calcium, inorganic phosphate, and pH on isometric force in single skinned cardiomyocytes from donor and failing human hearts. / Van Der Velden, J.; Klein, L. J.; Zaremba, R.; Boontje, N. M.; Huybregts, M. A.J.M.; Stooker, W.; Eijsman, L.; De Jong, J. W.; Visser, C. A.; Visser, F. C.; Stienen, G. J.M.

In: Circulation, Vol. 104, No. 10, 04.09.2001, p. 1140-1146.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Effects of calcium, inorganic phosphate, and pH on isometric force in single skinned cardiomyocytes from donor and failing human hearts

AU - Van Der Velden, J.

AU - Klein, L. J.

AU - Zaremba, R.

AU - Boontje, N. M.

AU - Huybregts, M. A.J.M.

AU - Stooker, W.

AU - Eijsman, L.

AU - De Jong, J. W.

AU - Visser, C. A.

AU - Visser, F. C.

AU - Stienen, G. J.M.

PY - 2001/9/4

Y1 - 2001/9/4

N2 - Background - During ischemia, the intracellular calcium and inorganic phosphate (Pi) concentrations rise and pH falls. We investigated the effects of these changes on force development in donor and failing human hearts to determine if altered contractile protein composition during heart failure changes the myocardial response to Ca2+, Pi, and pH. Methods and Results - Isometric force was studied in mechanically isolated Triton-skinned single myocytes from left ventricular myocardium. Force declined with added Pi to 0.33±0.02 of the control force (pH 7.1, 0 mmol/L Pi) at 30 mmol/L Pi and increased with pH from 0.64±0.03 at pH 6.2 to 1.27±0.02 at pH 7.4. Force dependency on Pi and pH did not differ between donor and failing hearts. Incubation of myocytes in a Pi-containing activating solution caused a potentiation of force, which was larger at submaximal than at maximal [Ca2+]. Ca2+ sensitivity of force was similar in donor hearts and hearts with moderate cardiac disease, but in end-stage failing myocardium it was significantly increased. The degree of myosin light chain 2 phosphorylation was significantly decreased in end-stage failing compared with donor myocardium, resulting in an inverse correlation between Ca2+ responsiveness of force and myosin light chain 2 phosphorylation. Conclusions - Our results indicate that contractile protein alterations in human end-stage heart failure alter Ca2+ responsiveness of force but do not affect the force-generating capacity of the cross-bridges or its Pi and pH dependence. In end-stage failing myocardium, the reduction in force by changes in pH and [Pi] at submaximal [Ca2+] may even be less than in donor hearts because of the increased Ca2+ responsiveness.

AB - Background - During ischemia, the intracellular calcium and inorganic phosphate (Pi) concentrations rise and pH falls. We investigated the effects of these changes on force development in donor and failing human hearts to determine if altered contractile protein composition during heart failure changes the myocardial response to Ca2+, Pi, and pH. Methods and Results - Isometric force was studied in mechanically isolated Triton-skinned single myocytes from left ventricular myocardium. Force declined with added Pi to 0.33±0.02 of the control force (pH 7.1, 0 mmol/L Pi) at 30 mmol/L Pi and increased with pH from 0.64±0.03 at pH 6.2 to 1.27±0.02 at pH 7.4. Force dependency on Pi and pH did not differ between donor and failing hearts. Incubation of myocytes in a Pi-containing activating solution caused a potentiation of force, which was larger at submaximal than at maximal [Ca2+]. Ca2+ sensitivity of force was similar in donor hearts and hearts with moderate cardiac disease, but in end-stage failing myocardium it was significantly increased. The degree of myosin light chain 2 phosphorylation was significantly decreased in end-stage failing compared with donor myocardium, resulting in an inverse correlation between Ca2+ responsiveness of force and myosin light chain 2 phosphorylation. Conclusions - Our results indicate that contractile protein alterations in human end-stage heart failure alter Ca2+ responsiveness of force but do not affect the force-generating capacity of the cross-bridges or its Pi and pH dependence. In end-stage failing myocardium, the reduction in force by changes in pH and [Pi] at submaximal [Ca2+] may even be less than in donor hearts because of the increased Ca2+ responsiveness.

KW - Contractility

KW - Heart failure

KW - Ischemia

KW - Myocytes

KW - Proteins

UR - http://www.scopus.com/inward/record.url?scp=0035806920&partnerID=8YFLogxK

U2 - 10.1161/hc3501.095485

DO - 10.1161/hc3501.095485

M3 - Article

VL - 104

SP - 1140

EP - 1146

JO - Circulation

JF - Circulation

SN - 0009-7322

IS - 10

ER -