Model of calcium-induced calcium release mechanism in cardiac cells

A model with which to elucidate the mechanism of Ca(2+) release from, and Ca(2+) loading in the sarcoplasmic reticulum (SR) by Ca(2+) current (I Ca) in cardiac cells is proposed. The SR is assumed to be comprised of three functional subcompartments: (1) the main calcium store (MCS), which contains most of the calcium (both free and bound); (2) the releasable terminal (RT), which contains the calcium readily available for release; and (3) the longitudinal network of the SR (LSR), which sequesters and the transfers the sarcoplasmic calcium to the RT. A rapid increase of the Ca(2+) concentration at the outer surface of the SR (Cae) due to the fast component of I(Ca) activates and inactivates this surface, inducing the release of Ca(2+) from the RT to the sarcoplasmic space. The RT in turn is further activated and inactivated by a increase in the concentration of sarcoplasmic Ca(2+). The Ca(2+) in the sarcoplasmic space is then sequestered by the LSR, leading to the reactivation of the RT. Further increase of Cae due to the slow component of I(Ca) enhances the entry of Ca(2+) into the MCS to be bound by the binding substance. The free Ca(2+) released from the Ca-binding substance complex is transferred to the RT for subsequent release. The activation, inactivation and reactivation are Ca(2+)-mediated and time-dependent. The proposed model yields simulation of the many events qualitatively similar to those observed experimentally in skinned cardiac cells.