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J Appl Physiol 92: 1506-1514, 2002. First published December 7, 2001; doi:10.1152/japplphysiol.00095.2001
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Vol. 92, Issue 4, 1506-1514, April 2002

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

Paige C. Geiger1,2, Mark J. Cody1, Young Soo Han1, Larry W. Hunter1, Wen-Zhi Zhan1, and Gary C. Sieck1,2

Departments of 1 Anesthesiology and 2 Physiology and Biophysics, Mayo Clinic and Foundation, Rochester, Minnesota 55905

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.

thyroid hormone levels; skinned fibers; myosin heavy chain content; force per cross bridge


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