Rate of Tension Development in Cardiac Muscle Varies With Level of Activator Calcium

Abstract

Abstract In skeletal muscle, the rate of transition from weakly bound to force-generating crossbridge states increases as calcium concentration is increased. To examine possible calcium sensitivity of this transition in cardiac muscle, we determined the kinetics of isometric tension development during steady activation in detergent-permeabilized rat ventricular trabeculae (n=7) over a range of calcium concentrations. Force-generating crossbridges in activated trabeculae were disrupted by a brief, rapid release and restretch equivalent to 20% muscle length (15°C), which resulted in a subsequent phase of tension redevelopment that was well fit by a monoexponential function (rate constant, k tr ). Sarcomere length was monitored by laser diffraction and held constant during tension redevelopment by an iterative adaptive feedback control system. The k tr increased from 3.6±0.8 s −1 at the lowest calcium concentration studied (pCa 5.9) to 9.5±1.3 s −1 during maximal activation (pCa 4.5). The relationship between relative k tr and relative tension was approximately linear over a wide range of [Ca 2+ ] ( r 2 =.94). This result differs quantitatively from results in skeletal muscle, in which k tr is sensitive to [Ca 2+ ] primarily at higher activation levels. This observation is also inconsistent with a recent suggestion that the rate of force development in living myocardium is independent of the activation level. Our results in skinned myocardium can be explained by a model in which calcium is a graded regulator of both the extent and rate of binding of force-generating crossbridges to the thin filament.