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Model of calcium-induced calcium release mechanism in cardiac cells

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Abstract

A model with which to elucidate the mechanism of Ca2+ release from, and Ca2+ loading in the sarcoplasmic reticulum (SR) by Ca2+ 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 Ca2+ concentration at the outer surface of the SR (Cae) due to the fast component ofI Ca activates and inactivates this surface, inducing the release of Ca2+ from the RT to the sarcoplasmic space. The RT in turn is further activated and inactivated by a increase in the concentration of sarcoplasmic Ca2+. The Ca2+ 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 ofI Ca enhances the entry of Ca2+ into the MCS to be bound by the binding substance. The free Ca2+ released from the Ca-binding substance complex is transferred to the RT for subsequent release. The activation, inactivation and reactivation are Ca2+-mediated and time-dependent. The proposed model yields simulation of the many events qualitatively similar to those observed experimentally in skinned cardiac cells.

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Authors and Affiliations

  1. Department of Physiology and Biophysics, Dalhousie University, B3H 4H7, Halifax, Nova Scotia, Canada

    Alan Y. K. Wong

  2. Department of Physiology, Medical College of Virginia, 23298, Richmond, VA, U.S.A.

    Alexandre Fabiato

  3. Center for Bioengineering, University of Washington, Seattle, Washington, U.S.A.

    James B. Bassingthwaighthe

Authors
  1. Alan Y. K. Wong
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  2. Alexandre Fabiato
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  3. James B. Bassingthwaighthe
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Wong, A.Y.K., Fabiato, A. & Bassingthwaighthe, J.B. Model of calcium-induced calcium release mechanism in cardiac cells. Bltn Mathcal Biology 54, 95–116 (1992). https://doi.org/10.1007/BF02458622

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  • DOI: https://doi.org/10.1007/BF02458622

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