title: Effect of heart failure on skeletal muscle myofibrillar protein content, isoform expression and calcium sensitivity.
abstract: BACKGROUND
  Alterations in skeletal muscle with heart failure contribute to exercise intolerance and physical disability. The majority of studies to date have examined abnormalities in skeletal muscle oxidative capacity and mitochondrial function. In contrast, less information is available regarding the effect of heart failure on myofibrillar protein metabolism and function. To address this issue, we examined the effect of heart failure on skeletal muscle myofibrillar protein content, isoform distribution and Ca2+ sensitivity.
  
  
  METHODS
  We measured skeletal muscle myosin heavy chain (MHC) and actin protein content and MHC isoform distribution in soleus (SOL), extensor digitorum longus (EDL), plantaris (PL) and diaphragm (DIA) muscles and myofibrillar Ca2+ sensitivity in EDL muscles from Dahl salt-sensitive rats with (high-salt fed: HS; n=10) or without heart failure (low-salt fed: LS; n=8) and assessed the relationship of these variables to markers of disease severity.
  
  
  RESULTS
  No differences in muscle mass were found. Similarly, no differences in MHC (mean+/-SE; SOL: 1353+/-29 vs. 1247+/-52; EDL: 1471+/-31 vs. 1441+/-31; PL: 1207+/-66 vs. 1286+/-36; DIA: 1166+/-42 vs. 1239+/-26 AU/microg protein) or actin (EDL: 348+/-13 vs. 358+/-19; PL: 245+/-20 vs. 242+/-9; DIA: 383+/-9 vs. 376+/-17 AU/microg protein) protein content or the actin-to-MHC ratio were observed, with the exception of lower (P<0.01) actin content in the soleus of LS rats (352+/-7 vs. 310+/-8 AU/microg protein). MHC isoform expression (I, IIa, IIx, IIb) did not differ between groups in SOL (I: 89+/-1% vs. 85+/-2%; IIa: 11+/-1% vs. 15+/-2%), EDL (IIx: 43+/-10% vs. 38+/-10%; IIb: 57+/-10% vs. 62+/-10%), PL (I: 6+/-4% vs. 3+/-3%; IIa: 1+/-1% vs. 1+/-1%; IIx: 31+/-3% vs. 26+/-4%; IIb: 62+/-5% vs. 71+/-6%) or DIA (I: 43+/-6% vs. 36+/-6 %; IIa: 9+/-1% vs. 7+/-1%; IIx: 47+/-6% vs. 56+/-7%; IIb: 2+/-1% vs. 1+/-0.5%) muscles. Moreover, heart failure did not affect the Ca2+ sensitivity (i.e., pCa50) of extensor digitorum longus myofilaments (5.68+/-0.11 vs. 5.65+/-0.09). Finally, MHC and actin content, MHC isoform distribution and myofibrillar Ca2+ sensitivity were not related to markers of disease severity.
  
  
  CONCLUSIONS
  Our results show that this animal model of heart failure is not characterized by alterations in the quantity or isoform distribution of key skeletal muscle myofibrillar proteins or the Ca2+ sensitivity of isometric force production. These findings suggest that alterations in skeletal muscle myofibrillar protein metabolism do not develop in parallel with myocardial failure in the Dahl salt-sensitive rat.
authors.affiliation: Department of Medicine, University of Vermont, Burlington, VT 05405, United States. mtoth@zoo.uvm.edu
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Toth
authors.forename: Bradley M
authors.initials: BM
authors.lastname: Palmer
authors.forename: Martin M
authors.initials: MM
authors.lastname: LeWinter
mesh_terms: D000199:Actins / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D006333:Heart Failure / Q000378:metabolism* / Q000503:physiopathology; D006352:Heart Ventricles / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D009210:Myofibrils / Q000187:drug effects / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000187:drug effects / Q000378:metabolism*; D020033:Protein Isoforms / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D020303:Rats, Inbred Dahl; D012982:Sodium, Dietary / Q000008:administration & dosage
chemical_list: D000199:Actins; D020033:Protein Isoforms; D012982:Sodium, Dietary; D018995:Myosin Heavy Chains; D002118:Calcium