Abstract
The Frank-Starling mechanism of the heart is based on the intrinsic ability of cardiac muscle that produces higher active force at a longer length (i.e., length-dependent activation). We have reported that the giant elastic protein titin (also known as connectin) performs as one of the triggering factors in length-dependent activation. In the present study, we tested whether length-dependent activation is regulated at the thin filament level by using our quasi-complete troponin (Tn) exchange technique. Reconstitution of thin filaments with fast skeletal troponin (sTn; prepared form rabbit psoas muscle) attenuated length-dependent activation in skinned porcine left ventricular muscle. Then, to investigate the effect of troponin exchange on cross-bridge kinetics, we measured the rate of force redevelopment (ktr) in both control and sTn-reconstituted cardiac muscles. ktr increased upon sTn reconstitution at submaximal levels, suggesting the acceleration of cross-bridge formation and, accordingly, a reduction in the fraction of resting cross-bridges that can potentially produce additional active force upon attachment to the thin filament. An increase in titin-based passive force, induced by manipulating the pre-history of stretch, enhanced length-dependent activation, in both control and sTn-reconstituted muscles. These results favor the interpretation that Tn plays an important role in the Frank-Starling mechanism of the heart via on-off switching of the thin filament state, in concert with titin-based regulation. [J Physiol Sci. 2008;58 Suppl:S67]
