The Role of the Sarcomere and Cytoskeleton in Cardiac Mechanotransduction

Abstract

The basic contractile unit of the cardiac myocyte is the sarcomere. Force develops as a result of the interaction of myosin heads with the actin thin filament. Actin filaments are directly connected to the Z line of the sarcomere, whereas myosin filaments are secured via the giant elastic protein titin. When cardiac muscle is stretched there is an immediate increase in contractility. This is an acute and fundamental cardiac adaptive response to an increase in demand. Evidence suggests that an increase in the probability of crossbridge formation, through titin strain and positive cooperative mechanisms, underlies the length-dependent activation of cardiac muscle. The sarcomere is connected to the sarcolemma by cytoskeletal components which link the Z-line with the membrane-spanning integrins and dystroglycan complex. Integrins and dystroglycan, in turn, bind to components of the extracellular matrix, such as laminin, which sheath the cardiac myocyte. Connections also exist between Z-line and nucleus via the intermediate filament protein desmin. The intracellular connections between the Z-line of the sarcomere and the sarcolemma allow transmission of force developed by the myofilaments. However, the physical pathway that links the extracellular matrix, membrane-spanning proteins, and the cell interior also plays a fundamental role in mechanotransduction. These links allow the cell to sense and respond to mechanical stimuli through connections with the cytoskeleton and activation of signalling cascades.