Effects of hypothyroidism on maximum specific force in rat diaphragm muscle fibers

Paige C. Geiger, Mark J. Cody, Young Soo Han, Larry W. Hunter, Wen Zhi Zhan, Gary C. Sieck

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

We hypothesized that 1) hypothyroidism (Hyp) decreases myosin heavy chain (MHC) content per half-sarcomere in diaphragm muscle (Diam) fibers, 2) Hyp decreases the maximum specific force (Fmax) of Diam fibers because of the reduction in MHC content per half-sarcomere, and 3) Hyp affects MHC content per half-sarcomere and Fmax to a greater extent in fibers expressing MHC type 2X (MHC2X) and/or MHC type 2B (MHC2B). Studies were performed on single Triton X-permeabilized fibers activated at pCa 4.0. MHC content per half-sarcomere was determined by densitometric analysis of SDS-polyacrylamide gels and comparison with a standard curve of known MHC concentrations. After 3 wk of Hyp, MHC content per half-sarcomere was reduced in fibers expressing MHC2X and/or MHC2B. On the basis of electron-microscopic analysis, this reduction in MHC content was also reflected by a decrease in myofibrillar volume density and thick filament density. Hyp decreased Fmax across all MHC isoforms; however, the greatest decrease occurred in fibers expressing fast MHC isoforms (∼40 vs. ∼20% for fibers expressing slow MHC isoforms). When normalized for MHC content per half-sarcomere, force generated by Hyp fibers expressing MHC2A was reduced compared with control fibers, whereas force per half-sarcomere MHC content was higher for fibers expressing MHC2X and/or MHC2B in the Hyp Diam than for controls. These results indicate that the effect of Hyp is more pronounced on fibers expressing MHC2X and/or MHC2B and that the reduction of Fmax with Hyp may be at least partially attributed to a decrease in MHC content per half-sarcomere but not to changes in force per cross bridge.

Original languageEnglish (US)
Pages (from-to)1506-1514
Number of pages9
JournalJournal of applied physiology
Volume92
Issue number4
DOIs
StatePublished - Jan 1 2002

Keywords

  • Force per cross bridge
  • Myosin heavy chain content
  • Skinned fibers
  • Thyroid hormone levels

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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    Geiger, P. C., Cody, M. J., Han, Y. S., Hunter, L. W., Zhan, W. Z., & Sieck, G. C. (2002). Effects of hypothyroidism on maximum specific force in rat diaphragm muscle fibers. Journal of applied physiology, 92(4), 1506-1514. https://doi.org/10.1152/japplphysiol.00095.2001