Age-dependent changes in myosin composition correlate with enhanced economy of contraction in guinea-pig hearts.
1. The composition of myosin heavy chains (MHCs) was investigated in young (1- to 8-week-old) and mature (9- to 26-week-old) guinea-pigs using two monoclonal antibodies directed specifically against alpha-MHC and beta-MHC. In addition, maximum force and the rate of ATP consumption during isometric contraction were measured in chemically skinned trabeculae taken from the same hearts. 2. An age-dependent shift in the MHC composition was found. The alpha-MHC fraction decreased from 0.17 +/- 0.02 (mean +/- S.E.M.; n = 24) in young to 0.04 +/- 0.01 (n = 43) in mature hearts. This shift was correlated with a decrease in tension cost (i.e. ATP consumption per second per trabecula volume/force per cross-sectional area) from 4.1 +/- 0.2 mmol kN-1 m-1 s-1 (n = 23) in young to 2.5 +/- 0.1 mmol kN-1 m-1 s-1 (n = 57) in mature hearts. 3. From the results it follows that the slow beta-MHC isoform, which predominates in hearts of mature guinea-pigs, is about 5 times more economical than the fast alpha-MHC isoform. Calcium sensitivity of force and ATP consumption decreased with age, but stabilized within a few weeks after birth. The pronounced dependence of cardiac energetics on MHC composition should be taken into account in long-term studies of cardiac overload.
van der Velden
J
J
Laboratory for Physiology, Institute for Cardiovascular Research, Free University, Amsterdam, The Netherlands. J.van_der_Velden.physiol@med.vu.nl
Moorman
A F
AF
Stienen
G J
GJ
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000375:Aging / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D000911:Antibodies, Monoclonal; D015153:Blotting, Western; D002118:Calcium / Q000502:physiology; D004591:Electrophoresis, Polyacrylamide Gel; D004734:Energy Metabolism / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology; D006352:Heart Ventricles / Q000378:metabolism; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000737:chemistry / Q000378:metabolism; D009218:Myosins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D016276:Ventricular Function
D000911:Antibodies, Monoclonal; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases; D018995:Myosin Heavy Chains; D009218:Myosins; D002118:Calcium