Effects of hypothyroidism on maximum specific force in rat diaphragm muscle fibers.
We hypothesized that 1) hypothyroidism (Hyp) decreases myosin heavy chain (MHC) content per half-sarcomere in diaphragm muscle (Dia(m)) fibers, 2) Hyp decreases the maximum specific force (F(max)) of Dia(m) fibers because of the reduction in MHC content per half-sarcomere, and 3) Hyp affects MHC content per half-sarcomere and F(max) to a greater extent in fibers expressing MHC type 2X (MHC(2X)) and/or MHC type 2B (MHC(2B)). 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 MHC(2X) and/or MHC(2B). 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 F(max) across all MHC isoforms; however, the greatest decrease occurred in fibers expressing fast MHC isoforms (approximately 40 vs. approximately 20% for fibers expressing slow MHC isoforms). When normalized for MHC content per half-sarcomere, force generated by Hyp fibers expressing MHC(2A) was reduced compared with control fibers, whereas force per half-sarcomere MHC content was higher for fibers expressing MHC(2X) and/or MHC(2B) in the Hyp Dia(m) than for controls. These results indicate that the effect of Hyp is more pronounced on fibers expressing MHC(2X) and/or MHC(2B) and that the reduction of F(max) 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.
Geiger
Paige C
PC
Department of Anesthesiology, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
Cody
Mark J
MJ
Han
Young Soo
YS
Hunter
Larry W
LW
Zhan
Wen-Zhi
WZ
Sieck
Gary C
GC
D000818:Animals; D001835:Body Weight; D003432:Cross-Linking Reagents / Q000032:analysis / Q000378:metabolism; D003964:Diaphragm / Q000166:cytology / Q000502:physiology*; D007037:Hypothyroidism / Q000503:physiopathology*; D007536:Isomerism; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000737:chemistry / Q000502:physiology*; D018995:Myosin Heavy Chains / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012518:Sarcomeres / Q000737:chemistry / Q000378:metabolism; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
D003432:Cross-Linking Reagents; D014284:Triiodothyronine; D018995:Myosin Heavy Chains; D013974:Thyroxine