Age-dependent changes in myosin composition correlate with enhanced economy of contraction in guinea-pig hearts

摘要

class="enumerated" style="list-style-type:decimal">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 α-MHC and β-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.An age-dependent shift in the MHC composition was found. The α-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.From the results it follows that the slow β-MHC isoform, which predominates in hearts of mature guinea-pigs, is about 5 times more economical than the fast α-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.