RATE OF TENSION DEVELOPMENT IN CARDIAC-MUSCLE VARIES WITH LEVEL OF ACTIVATOR CALCIUM

In skeletal muscle, the rate of transition from weakly bound to force- generating crossbridge states increases as calcium concentration is in creased. To examine possible calcium sensitivity of this transition in cardiac muscle, we determined the kinetics of isometric tension devel opment during steady activation in detergent-permeabilized rat ventric ular trabeculae (n=7) over a range of calcium concentrations. Force-ge nerating crossbridges in activated trabeculae were disrupted by a brie f, rapid release and restretch equivalent to 20% muscle length (15 deg rees 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 consta nt during tension redevelopment by an iterative adaptive feedback cont rol system. The k(tr) increased from 3.6+/-0.8 s(-1) at the lowest cal cium 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 rel ative tension was approximately linear over a wide range of [Ca2+] (r( 2)=.94). This result differs quantitatively from results in skeletal m uscle, in which k(tr) is sensitive to [Ca2+] primarily at higher activ ation levels. This observation is also inconsistent with a recent sugg estion that the rate of force development in living myocardium is inde pendent of the activation level. Our results in skinned myocardium can be explained by a model in which calcium is a graded regulator of bot h the extent and rate of binding of force-generating crossbridges to t he thin filament.