Different behaviour of the non-sarcomeric cytoskeleton in neonatal and adult rat cardiomyocytes

Abstract

Neonatal and adult rat cardiomyocytes display differences when isolated and cultured in vitro. Whereas cells obtained from juvenile hearts adapt quite rapidly as judged by their beating, cells from adult animals undergo a complex degeneration-regeneration process of their myofibrillar apparatus. These differences are also reflected by a distinct sensitivity to drugs that affect the non-sarcomeric cytoskeleton. After long-term treatment with nocodazole, which disassembles microtubules, neonatal rat cardiomyocytes (NRC) remain relatively unaffected, whereas adult rat cardiomyocytes (ARC) are unable to spread on the substrate or to undergo the remodelling process of their myofibrils. If microfilaments are destroyed by cytochalasin D, neither NRC nor ARC spread, and they lose the capacity to assemble new myofibrils. The effects of drug treatment with both cytochalasin and nocodazole, respectively, were reversible, since normal myofibrillogenesis took place after the cells had been washed and cultivated in standard medium for 4 days. This study demonstrates that microfilaments are essential for assembly of new sarcomeres in vitro, and underlines intrinsic differences between NRC and ARC in their requirement for intact microtubules. Adult cardiomyocytes have lost a certain degree of flexibility due to their longer adaptation to the specific situation in the heart, whereas cardiomyocytes isolated from neonatal animals can maintain and assemble myofibrils in vitro even after their microtubules were destroyed.