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.