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

Abstract

To elucidate the essential features of Ca²⁺ release from the terminal sac (TS) of the sarcoplasmic reticulum (SR) in heart muscle, a model for Ca²⁺ release from the TS was constructed based on the mechanism of Ca²⁺-induced Ca²⁺-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 Ca²⁺ release channel in the TS. Ca²⁺ moves from compartment to compartment by simple diffusion and is taken up from each compartment by the tubular SR via Ca²⁺-ATPase. Simulation based on one-dimensional diffusion of Ca²⁺ showed that TS Ca²⁺ release is smoothly graded over a wide range of levels of Ca²⁺ influx when the TS is moderately loaded with Ca²⁺, and it occurs in an all-or-none manner when the TS is heavily loaded with Ca²⁺. The graded TS Ca²⁺ release was generated with both local and uniform Ca²⁺ influx into the cytoplasm. The propagation of the Ca²⁺ wave was simulated by the use of a model consisting of several longitudinally consecutive sarcomeres with TS heavily loaded with Ca²⁺. Mechanical alternans, characterized by an alternation of small and large twitches, was also simulated by applying Ca²⁺ influx at an appropriate interval during which Ca²⁺ was replenished to the TS at a constant rate. Thus the present model reflects several important aspects of TS Ca²⁺ release in heart muscle.