Model of calcium-induced calcium release mechanism in cardiac cells

Abstract

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 (Ca e ) 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 Ca e 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.

A model of calcium-induced calcium release from the sarcoplasmic reticulum in the smooth muscle cell and its investigation by mathematical modeling

“…Several similar models have been published in the literature [3,6,[27][28][29][30]32], the purpose of which was to achieve agreement with the experiment. Therefore, these models took into account practically all ideas about calcium homeostasis in the cell and covered all possible participants of this process.…”

“…Various assumptions have been made in scientific literature about possible mechanisms of activation and inhibition by calcium cations of channels and pumps on PM and SR [3,5,7,8,11,12,17,24,26,27], about the mechanisms responsible for SOCЕ [2,8,12,[20][21][22]24], theoretical models have been constructed to reproduce some of the observed experimental results [3,6,[27][28][29][30][31][32], but so far the processes discussed above remain largely unexplained.…”

Multiscale Modeling of Cardiac Cellular Energetics

“…The multiscale cardiac and cardiovascula‐respiratory system model brings together many transport models1,9,31–50 with work by us on cardiac cell modeling3,4,51–62 and by many others, 7,8,17,18,25,63‐68 in models incorporating both cardiac and endothelial cell uptake and metabolism;69‐75 and for accounting for regional flow heterogeneities 5,6,37,76‐80. Many of these are available at our Web site.…”

Toward Modeling the Human Physionome

“…They are for the most part unrelated to each other: models for the spread of excitation over a layer of epicardium [3], models for purine metabolism and high energy phosphates [4,5], models for flow distribution throughout the heart [6], models for the action potential [7], models for fatty acid metabolism [8,9], models of excitation-contraction coupling at the cellular level [10][11][12], models for calcium release from the SR [13], models for vasoregulation in the heart [14] and in skeletal muscle [15].…”