Abstract
At the basis of the Frank-Starling mechanism of the heart is the intrinsic ability of the contractile system to produce active force in response to stretch. It has been reported that length-dependent activation is, at least in part, modulated via interfilament lattice spacing reduction due to titin-based passive force (e.g., Fukuda et al., J. Physiol. 553, 147-154, 2003). In the current study, we examined whether or not length-dependent activation is modulated at the thin filament level. We used skinned porcine ventricular muscle that had been treated with 1% (w/v) Triton X-100. An increase in sarcomere length (SL) from 1.9 to 2.3 μm exerted a marked increase in Ca2+ sensitivity with a concomitant increase in passive force. The SL-dependent increase in Ca2+ sensitivity was markedly attenuated by perfusing preparations with rigor solution containing exogenous fast skeletal troponin (T-I-C complex; rabbit psoas muscle), with little or no effects on passive force. The magnitude of SL dependency was similar to what was observed in rabbit psoas muscle. Our SDS-PAGE analyses showed that endogenous cardiac troponin subunits were replaced with skeletal counterparts by ∼100% and that titin was not degraded upon troponin exchange. These results suggest that, presumably downstream of titin-based lattice spacing reduction, length-dependent activation is modulated at the thin filament level. [J Physiol Sci. 2006;56 Suppl:S147]
