Extent of radial sarcomere coupling revealed in passively stretched cardiac myocytes

The complex geometry of the heart leads to a time-varying and nonuniform distribution of stress and strain on the myocardium during the cardiac cycle. This study investigated the sarcomere length and striation registration behavior resulting from a gradient of strain imposed on the cytoskeleton of isolated cardiac myocytes. Within a myocyte, sarcomeres are organized into domains separated by strips of mitochondria and nuclei. Sarcomeres are interconnected radially at the Z-disc by the exosarcomeric cytoskeleton, composed primarily of the intermediate filament desmin. Chemically skinned myocytes isolated from adult rat hearts were attached using to concentric double-barreled pipettes in such a way as to induce a gradient of applied strain across the width of the cell. At rest lengths, there was variation in the sarcomere length between domains of attached cells. Upon stretch, most domains exhibited proportional increases in sarcomere length, with the initial differences being maintained. However, some domains did not behave in synchrony with the others at shorter sarcomere lengths. Thus, the coupling between sarcomeric domains can allow for a non-linear relationship between sarcomere length and strain. Sarcomeres were tightly coupled in the radial direction within a single domain, but striation mis-registration of up to 0.20 micron between domains was induced by stretch. This indicates the looser nature of the cytoskeletal coupling between domains compared to that within domains. Thus, cardiac myocytes are not rigid functional units, but composite structures whose components consist of functionally semi-independent domains tethered by the cytoskeletal intermediate filament lattice.