Age-dependent changes in contraction and regional myocardial myosin heavy chain isoform expression in rats.

Abstract

The goals of this study were to measure the relative levels of the alpha- and beta-isoforms of myosin heavy chain (MHC-alpha and MHC-beta, respectively) in multiple, specific regions of the adult rat heart and to determine whether age-dependent changes in isoform levels in different regions are uniform. Relative amounts of MHC-alpha and MHC-beta were determined in right and left atria and left ventricular (LV) Purkinje fibers (PF), papillary muscles, trabeculae, and endo-, mid-, and epicardial regions at 2, 5, 10, 16, and 21 mo. PFs contained substantial amounts of myosin and were striated and capable of generating force and shortening on activation. Levels of MHC-beta increased in all LV compartments with age, especially between 2 and 5 mo. There was more MHC-beta in PFs than other LV sites. There were regional differences in the level of MHC-beta throughout the LV at all ages, and the rates of change within regions differed. Ca(2+)-activated tension in PFs and trabeculae was compared at 2 and 22 mo. PF tension was less than trabecula tension, and this difference may be explained by differences in MHC content. V(max) and tension-generating ability in PFs decreased with age. Maximal tension generated by trabeculae did not change during aging. A large proportion of the increase in the level of MHC-beta that is normally associated with aging occurs at a relatively early age in rat LV. PFs, with their small diameters and short diffusion distance, should be considered for skinned multicellular myocardial studies.