Muscle force and power input depends on the lattice spacing, i.e., distance between thick and thin filaments of muscle. It has been known for a long time that here is an enhancement of contractible activity for a given level of activation by Ca2e at longer muscle lengths. Although this is the primary regulatory mechanism in the working heart, its mechanism is unknown. We are testing to see if this is due to the filament being at the optimal lattice spacing by taking a number of measurements of lattice spacing at different muscle lengths, in both passive and active muscle and at various degrees of lattice compression by including high molecular weight polymers in the solution. We recently completed a first study which accurately mapped out the incremental change in lattice spacing in response to small length changes over the working range of the heart. These data will be tested to see if they are consistent with either constant volume or the lattice stability model described by Millman (Physiol. Rev. 78:359-391, 1998). We also completed preliminary studies using osmotic compression to shrink the filament lattice to its in vivo spacing as well as normal and mutant mice which express slow skeletal Troponin I. By combining these approaches with x-ray studies of contracting muscle and offline mechanical measurements of force as a function of calcium concentration, we will be able to clarify the role of lattice spacing in the enhanced sensitivity of cardiac muscle to calcium at long lengths.
