EXTENT OF RADIAL SARCOMERE COUPLING REVEALED IN PASSIVELY STRETCHED CARDIAC MYOCYTES

The complex geometry of the heart leads to a time-varying and nonunifo rm distribution of stress and strain on the myocardium during the card iac cycle. This study investigated the sarcomere length and striation registration behavior resulting from a gradient of strain imposed on t he cytoskeleton of isolated cardiac myocytes. Within a myocyte, sarcom eres are organized into domains separated by strips of mitochondria an d nuclei. Sarcomeres are interconnected radially at the Z-disc by the exosarcomeric cytoskeleton, composed primarily of the intermediate fil ament desmin. Chemically skinned myocytes isolated from adult rat hear ts were attached using to concentric double-barreled pipettes in such a way as to induce a gradient of applied strain across the width of th e cell. At rest lengths, there was variation in the sarcomere length b etween domains of attached cells. Upon stretch, most domains exhibited proportional increases in sarcomere length, with the initial differen ces being maintained. However, some domains did not behave in synchron y with the others at shorter sarcomere lengths. Thus, the coupling bet ween sarcomeric domains can allow for a non-linear relationship betwee n sarcomere length and strain. Sarcomeres were tightly coupled in the radial direction within a single domain, but striation mis-registratio n of up to 0.20 mu m between domains was induced by stretch. This indi cates the looser nature of the cytoskeletal coupling between domains c ompared to that within domains. Thus, cardiac myocytes are not rigid f unctional units, but composite structures whose components consist of functionally semi-independent domains tethered by the cytoskeletal int ermediate filament lattice. (C) 1997 Wiley-Liss, Inc.