Effect of extraction of myosin binding protein C on contractility of rat heart.
Human hearts with reduced or mutant myosin binding protein C (MyBP-C) undergo hypertrophy and dilation, suggesting that reduction or alteration of MyBP-C interferes with normal contraction. Extraction of 60-70% of MyBP-C over 1 h from a mechanically disrupted cardiac myocyte has been shown to increase Ca sensitivity but does not appear to impair development of maximum Ca-activated force (Fmax). To determine whether loss of MyBP-C over a longer period of time will decrease force development in a reversible manner, MyBP-C has been extracted from chemically skinned rat cardiac trabeculae for 1-4 h, and force production, Ca sensitivity, and thick filament structure were measured. Although extraction of MyBP-C for 1 h did not alter Fmax, after 4 h, myosin heads became disordered and Fmax decreased. At this point, incubation of the trabeculae with rat cardiac MyBP-C in a relaxing solution reversed the decline in Fmax and most of the change in order of myosin heads. Extraction of MyBP-C appears to produce a change in the orientation of myosin heads that is associated with a decreased ability of the contractile system to develop force.
Kulikovskaya
I
I
Department of Physiology, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6085, USA.
McClellan
G
G
Levine
R
R
Winegrad
S
S
D000818:Animals; D002118:Calcium / Q000378:metabolism; D009202:Cardiomyopathies / Q000503:physiopathology; D002352:Carrier Proteins / Q000302:isolation & purification / Q000494:pharmacology / Q000502:physiology*; D003599:Cytoskeleton / Q000187:drug effects / Q000502:physiology*; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000099163:Myosin Binding Protein C
D002118:Calcium; D002352:Carrier Proteins; D000099163:Myosin Binding Protein C