Contractile protein function in failing and nonfailing human myocardium

Skeletal muscle weakness is a common finding in patients with chronic heart failure (CHF). This functional deficit cannot be accounted for by muscle atrophy alone, suggesting that the syndrome of heart failure induces a myopathy in the skeletal musculature. To determine whether decrements in muscle performance are related to alterations in contractile protein function, biopsies were obtained from the vastus lateralis muscle of four CHF patients and four control patients. CHF patients exhibited reduced peak aerobic capacity and knee extensor muscle strength. Decrements in whole muscle strength persisted after statistical control for muscle size. Thin filaments and myosin were isolated from biopsies and mechanically assessed using the in vitro motility assay. Isolated skeletal muscle thin-filament function, however, did not differ between CHF patients and controls with respect to unloaded shortening velocity, calcium sensitivity, or maximal force. Similarly, no difference in maximal force or unloaded shortening velocity of isolated myosin was observed between CHF patients and controls. From these results, we conclude that skeletal contractile protein function is unaltered in CHF patients. Other factors, such as a decrease in total muscle myosin content, are likely contributors to the skeletal muscle strength deficit of heart failure.

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Identification and Distribution of the Calcium-Dependent Regulator Protein in Human Platelet Preparations

10.1055/s-0039-1684462 ◽

1979 ◽

Author(s):

S.N. Levine ◽

A.L. Steiner ◽

G.C. White

Keyword(s):

Protein Function ◽

Mammalian Cells ◽

Calcium Metabolism ◽

Specific Activity ◽

Polyacrylamide Gel Electrophoresis ◽

Microtubule Assembly ◽

Contractile Protein ◽

Calcium Dependent ◽

Regulator Protein

Calcium-dependent regulator protein (CDR) is a 17,000 molecular weight polypeptide which has been demonstrated in a number of mammalian cells and has been shown to 1) modulate activation of adenylate cyclase activity, 2) stimulate erythrocyte membrane (Ca++/Mg++) ATPase activity, 3) stimulate cardiac microsomal calcium uptake, 4) activate smooth muscle myosin light chain kinase activity, and 5) regulate microtubule assembly and disassembly. Because of the role of CDR in calcium metabolism and contractile protein function, we have examined the presence and subcellular distribution of this protein in preparations of human platelets. CDR was quantified using a two-step phosphodiesterase assay (Kakiuchi et al, PNAS 70:3526, 1973). Bovine brain CDR which was homogeneous by SDS polyacrylamide gel electrophoresis was used as a standard. Whole platelets contained approximately 4.4 ug CDR/mg platelet protein. When platelets were fractionated by glycerol osmoticlysis followed by separation on 27% sucrose, the soluble portion had the highest specific activity and the membrane fraction, the lowest. These studies demonstrate the presence of CDR in platelets and indicate subcellular compart-mentalization of the protein. The role of CDR in calcium metabolism and contractile protein function in platelets is currently under study, (AHA 78-1215/NIH AM17438, DE02668)

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