Document Detail

Effect of cardiac myosin binding protein-C on mechanoenergetics in mouse myocardium.
MedLine Citation:
PMID:  15155526     Owner:  NLM     Status:  MEDLINE    
We examined the effect of cardiac myosin binding protein-C (cMyBP-C) on contractile efficiency in isovolumically contracting left ventricle (LV) and on internal viscosity and oscillatory work production in skinned myocardial strips. A 6-week diet of 0.15% 6-n-propyl-2-thiouracil (PTU) was fed to wild-type (+/+(PTU)) and homozygous-truncated cMyBP-C (t/t(PTU)) mice starting at age approximately 8 weeks and leading to a myosin heavy chain (MHC) isoform profile of 10% alpha-MHC and 90% beta-MHC in both groups. Western blot analysis confirmed that cMyBP-C was present in the +/+(PTU) and effectively absent in the t/t(PTU). Total LV mechanical energy per beat was quantified as pressure-volume area (PVA). O2 consumption (Vo2) per beat was plotted against PVA at varying LV volumes. The reciprocal of the slope of the linear Vo2-PVA relation represents the contractile efficiency of converting O2 to mechanical energy. Contractile efficiency was significantly enhanced in t/t(PTU) (26.1+/-2.6%) compared with +/+(PTU) (17.1+/-1.6%). In skinned myocardial strips, maximum isometric tension was similar in t/t(PTU) (18.7+/-2.1 mN x mm(-2)) and +/+(PTU) (21.9+/-4.0 mN x mm(-2)), but maximum oscillatory work induced by sinusoidal length perturbations occurred at higher frequencies in t/t(PTU) (7.31+/-1.17 Hz) compared with +/+(PTU) (4.48+/-0.60 Hz) and was significantly more sensitive to phosphate concentration in the t/t(PTU). Under rigor conditions, the internal viscous load was significantly lower in the t/t(PTU) compared with +/+(PTU), ie, approximately 40% lower at 1 Hz. These results collectively suggest that contractile efficiency is enhanced in the t/t(PTU), probably through a reduced loss of mechanical energy by a viscous load normally provided by cMyBP-C and through a gain of phosphate-dependent oscillatory work normally inhibited by cMyBP-C.
Bradley M Palmer; Teruo Noguchi; Yuan Wang; John R Heim; Norman R Alpert; Patrick G Burgon; Christine E Seidman; J G Seidman; David W Maughan; Martin M LeWinter
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, U.S. Gov't, P.H.S.     Date:  2004-05-20
Journal Detail:
Title:  Circulation research     Volume:  94     ISSN:  1524-4571     ISO Abbreviation:  Circ. Res.     Publication Date:  2004 Jun 
Date Detail:
Created Date:  2004-06-25     Completed Date:  2004-12-20     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0047103     Medline TA:  Circ Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1615-22     Citation Subset:  IM    
Department of Molecular Physiology and Biophysics, University of Vermont College of Medicine, University of Vermont, Burlington, Vt 05405, USA.
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MeSH Terms
Actomyosin / physiology
Calcium Signaling
Carrier Proteins / genetics,  physiology*
Energy Metabolism
Isometric Contraction
Mice, Knockout
Microfilaments / physiology,  ultrastructure
Myocardial Contraction / physiology*
Myosin Heavy Chains / physiology
Oxygen Consumption
Phosphates / physiology
Propylthiouracil / toxicity
Ventricular Function
Grant Support
Reg. No./Substance:
0/Carrier Proteins; 0/Myosin Heavy Chains; 0/Phosphates; 0/myosin-binding protein C; 51-52-5/Propylthiouracil; 9013-26-7/Actomyosin

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