Abstract
We have explored the role of the giant elastic protein titin in the Frank-Starling mechanism of the heart by measuring the sarcomere length (SL) dependence of activation in skinned cardiac muscles with different titin-based passive stiffness characteristics. We studied muscle from the bovine left ventricle (BLV), which expresses a high level of a stiff titin isoform (N2B titin), and muscle from the bovine left atrium (BLA), which expresses more compliant titin isoforms (N2BA titins). Passive tension was also varied in each muscle type by manipulating the pre-history of stretch prior to activation. We found that the SL-dependent increases in Ca2+ sensitivity and maximal Ca2+-activated tension were markedly more pronounced when titin-based passive tension was high. Control experiments suggest that the greater SL dependency in BLV is unlikely due to differences in the contractile protein isoform composition. Small-angle X-ray experiments revealed that the SL dependence of reduction of interfilament lattice spacing is greater in BLV than in BLA, and that the lattice spacing is coupled with titin-based passive tension. These results support the notion that titin-based passive tension promotes actomyosin interaction by reducing the lattice spacing. This work indicates that titin may be a factor involved in the Frank-Starling mechanism of the heart by promoting actomyosin interaction in response to stretch. [Jpn J Physiol 55 Suppl:S119 (2005)]
