Model for the Regulation of Ca2+ Release from the Sarcoplasmic Reticulum in Heart Muscle.

To elucidate the essential features of Ca(2+) release from the terminal sac (TS) of the sarcoplasmic reticulum (SR) in heart muscle, a model for Ca(2+) release from the TS was constructed based on the mechanism of Ca(2+)-induced Ca(2+)-release by assuming a small TS volume. For numerical computation, we divided the cytoplasm in a half sarcomere into 50 compartments, one end of which faced the TS and determined the open probability of the Ca(2+) release channel in the TS. Ca(2+) moves from compartment to compartment by simple diffusion and is taken up from each compartment by the tubular SR via Ca(2+)-ATPase. Simulation based on one-dimensional diffusion of Ca(2+) showed that TS Ca(2+) release is smoothly graded over a wide range of levels of Ca(2+) influx when the TS is moderately loaded with Ca(2+), and it occurs in an all-or-none manner when the TS is heavily loaded with Ca(2+). The graded TS Ca(2+) release was generated with both local and uniform Ca(2+) influx into the cytoplasm. The propagation of the Ca(2+) wave was simulated by the use of a model consisting of several longitudinally consecutive sarcomeres with TS heavily loaded with Ca(2+). Mechanical alternans, characterized by an alternation of small and large twitches, was also simulated by applying Ca(2+) influx at an appropriate interval during which Ca(2+) was replenished to the TS at a constant rate. Thus the present model reflects several important aspects of TS Ca(2+) release in heart muscle.