Depression of force production and ATPase activity in different types of human skeletal muscle fibers from patients with chronic heart failure

P. Szentesi, M. A. Bekedam, B. J. Van Beek-Harmsen, W. J. Van Der Laarse, R. Zaremba, A. Boonstra, F. C. Visser, G. J.M. Stienen

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Isometric force production and ATPase activity were determined simultaneously in single human skeletal muscle fibers (n = 97) from five healthy volunteers and nine patients with chronic heart failure (CHF) at 20°C. The fibers were permeabilized by means of Triton X-100 (1% vol/vol). ATPase activity was determined by enzymatic coupling of ATP resynthesis to the oxidation of NADH. Calcium-activated actomyosin (AM) ATPase activity was obtained by subtracting the activity measured in relaxing (pCa = 9) solutions from that obtained in maximally activating (pCa = 4.4) solutions. Fiber type was determined on the basis of myosin heavy chain isoform composition by polyacrylamide SDS gel electrophoresis. AM ATPase activity per liter cell volume (±SE) in the control and patient group, respectively, amounted to 134 ± 24 and 77 ± 9 μM/s in type I fibers (n = 11 and 16), 248 ± 17 and 188 ± 13 μM/s in type IIA fibers (n = 14 and 32), 291 ± 29 and 126 ± 21 μM/s in type IIA/X fibers (n = 3 and 5), and 325 ± 32 and 205 ± 21 μM/s in type IIX fibers (n = 7 and 9). The maximal isometric force per cross-sectional area amounted to 64 ± 7 and 43 ± 5 kN/m2 in type I fibers, 86 ± 11 and 58 ± 4 kN/m2 in type IIA fibers, 85 ± 6 and 42 ± 9 kN/m2 in type IIA/X fibers, and 90 ± 5 and 59 ± 5 kN/m2 in type IIX fibers in the control and patient group, respectively. These results indicate that, in CHF patients, significant reductions occur in isometric force and AM ATPase activity but that tension cost for each fiber type remains the same. This suggests that, in skeletal muscle from CHF patients, a decline in density of contractile proteins takes place and/or a reduction in the rate of cross-bridge attachment of ∼30%, which exacerbates skeletal muscle weakness due to muscle atrophy.

Original languageEnglish
Pages (from-to)2189-2195
Number of pages7
JournalJournal of Applied Physiology
Volume99
Issue number6
DOIs
Publication statusPublished - Dec 1 2005

    Fingerprint

Keywords

  • Adenosine 5′-triphosphatase hydrolysis
  • Exercise capacity
  • Muscle contraction

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Szentesi, P., Bekedam, M. A., Van Beek-Harmsen, B. J., Van Der Laarse, W. J., Zaremba, R., Boonstra, A., Visser, F. C., & Stienen, G. J. M. (2005). Depression of force production and ATPase activity in different types of human skeletal muscle fibers from patients with chronic heart failure. Journal of Applied Physiology, 99(6), 2189-2195. https://doi.org/10.1152/japplphysiol.00542.2005