The length-dependence of calcium sensitivity in skinned rat ventricular trabeculae (calcium for 50% activation decreased from 7.71 to 3.77 microM as sarcomere length increased) accounts for the shape of the ascending limb in intact muscle.
The properties of the cardiac contractile machinery, including the length-dependence of calcium sensitivity, can account for much of the shape of the ascending limb in intact cardiac muscle.
To investigate the extent to which the properties of the cardiac myofibrils contribute to the length-force relation of cardiac muscle, we determined the sarcomere length-force relations for rat ventricular trabeculae both before and after the muscles were skinned with the detergent Triton X-100. Sarcomere length was measured continuously by laser diffraction. In the unskinned trabeculae stimulated at 0.2 Hz, the relation between active force and sarcomere length at an extracellular calcium concentration of 1.5 mM was curved away from the sarcomere length axis, with zero force at sarcomere length of 1.5-1.6 micron. At 0.3 mM calcium, the sarcomere length-force relation was curved toward the sarcomere length axis. Chemical skinning of the muscle with 1% Triton X-100 in a "relaxing solution" caused an increase in intensity and decrease in dispersion of the first order diffraction beam, indicating an increased uniformity of sarcomere length in the relaxed muscle. During calcium-regulated contractures in the skinned muscles, the central sarcomeres shortened by up to 20%. As the calcium concentration was increased over the range 1-50 microM, the relation between steady calcium-regulated force and sarcomere length shifted to higher force values and changed in shape in a manner similar to that observed for changes in extracellular calcium concentration before skinning. The sarcomere length-force relations for the intact muscles at an extracellular calcium concentration of 1.5 mM were similar to the curves at calcium concentration of 8.9 microM in the skinned preparations, whereas the curves at an extracellular calcium concentration of 0.3 mM in intact muscles fell between the relations at calcium concentrations of 2.7 and 4.3 microM in the skinned preparations. A factor contributing to the shape of the curves in the skinned muscle at submaximal calcium concentrations was that the calcium sensitivity of force production increased with increasing sarcomere length. The calcium concentration required for 50% activation decreased from 7.71 +/- 0.52 microM to 3.77 +/- 0.33 microM for an increase of sarcomere length from 1.75 to 2.15 micron. The slope of the force-calcium concentration relation increased from 2.82 to 4.54 with sarcomere length between 1.75 and 2.15 micron. This change in calcium sensitivity was seen over the entire range of sarcomere lengths corresponding to the ascending limb of the cardiac length-force relation. It is concluded that the properties of the cardiac contractile machinery (including the length-dependence of calcium sensitivity) can account for much of the shape of the ascending limb in intact cardiac muscle.
Kentish et al. (1986) studied Cardiac muscle physiology (rat right ventricle). Chemical skinning with 1% Triton X-100 and varying calcium concentrations vs. Intact (unskinned) trabeculae was evaluated on Sarcomere length-force relations. The length-dependence of calcium sensitivity in skinned rat ventricular trabeculae (calcium for 50% activation decreased from 7.71 to 3.77 microM as sarcomere length increased) accounts for the shape of the ascending limb in intact muscle.