Uncontrolled sarcomere shortening increases intracellular Ca2+ transient in rat cardiac trabeculae

Isolated cardiac muscle preparations suffer from damaged-end compliance that allows for substantial shortening of central sarcomeres during contractions in which the overall length of muscle is kept constant. The impact of uncontrolled sarcomere shortening during a twitch on the intracellular calcium transient in myocardium is unknown. Accordingly, in the present study we developed an iterative laser-diffraction feedback system that allowed for the accurate control of central-segment sarcomere length and simultaneous measurement of iontophoretically injected fura 2 fluorescence in isolated cardiac trabeculae. We compared fura 2 fluorescence signals recorded during regular twitches with twitches in which central sarcomere length (SL) was held constant by feedback control ("SL clamp" twitches). We found that uncontrolled sarcomere shortening was associated with a significant (P = 0.005) increase in the peak of the calcium transient and that the amount of this increase was directly correlated to the extent of central-segment sarcomere shortening (r2 = 0.92; P < 0.01). The time course of the calcium transient, however, was unaffected by the mode of contraction (P = 0.64). These findings have important implications for the interpretation of studies of myocardial calcium handling in which uncontrolled sarcomere shortening takes place during the twitch.