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Articles in PresS, published online ahead of print December 7, 2001
J Appl Physiol, 10.1152/jap.00095.2001
Submitted on January 30, 2001
Accepted on December 3, 2001
1 Anesthesiology, Mayo Clinic and Foundation, Rochester, MN, USA; Physiology and Biophysics, Mayo Clinic and Foundation, Rochester, MN, USA
2 Anesthesiology, Mayo Clinic and Foundation, Rochester, MN, USA
* To whom correspondence should be addressed. E-mail: Sieck.Gary{at}mayo.edu, lechtenberg.bettie@mayo.edu.
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 due to 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 MHC2X and/or MHC2B. Studies were performed on single Triton-X permeabilized fibers activated at a pCa (-log Ca2+ concentration) of 4.0. MHC content per half-sarcomere was determined by densitometric analysis of SDS-PAGE gels and comparison to a standard curve of known MHC concentrations. After 3 weeks of HYP, MHC content per half-sarcomere was reduced in fibers expressing MHC2X and/or MHC2B. Based on electron microscopic analysis, this reduction in MHC content was also reflected by a decrease in both 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 MHCSlow). When normalized for MHC content per half-sarcomere, force generated by HYP fibers expressing MHC2A was reduced compared with control fibers while force per half-sarcomere MHC content was higher for fibers expressing MHC2X and/or MHC2B in the HYP DIAm compared to 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.
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