Sarcolemmal calcium binding sites in heart: II. Mathematical model for diffusion of calcium released from the sarcoplasmic reticulum into the diadic region (original) (raw)

Summary

We present a model for predicting the temporal and spatial dependence of [Ca] in the cardiac subsarcolemmal diadic region (cleft), following Ca release from the “feet” of the sarcoplasmic reticulum. This region is modeled as a disc 10 nm thick, 430 nm in radius, with or without Ca binding sites and open at its periphery to the cytosol. [Ca] is computed for three diffusion coefficients (100, 20 and 4% of aqueous diffusion), following release of a 20-msec square pulse sufficient to produce 50% maximal contractile force, or repetitive release (400/min) of such pulses. Numerical solutions are obtained for the general diffusion/binding problem and analytic solutions for the case of no binding sites. For the middle value of diffusion coefficient, and in the absence of binding sites, [Ca] rises to ∼ 1.5 mm in 20-msec and then falls to ∼0.1 μm in < 3 msec. Adding binding sites reduces peak [Ca] to ∼0.6 mm but prolongs its decline, requiring ∼200 msec to reach 20 μm. For repetitive release [Ca] is > 100 μm for roughly half of each cycle. Two major implications of the predicted [Ca] are: (i) The effect of Ca binding sites on [Ca] will cause Ca efflux from the cleft via the NaCa exchanger (K m (Ca)≈ 20 μm) to continue at a significant level for > 200 msec, (ii) The time constant for inactivation of release from the “feet” must be much greater than for activation if Cainduced Ca release is to continue for > 1–2 msec.

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  1. Jan A. Posit
    Present address: Institute of Biomembranes, State University Utrecht, 3584, Utrecht, CH, The Netherlands

Authors and Affiliations

  1. Departments of Biomathematics and Physiology, University of California at Los Angeles School of Medicine, 90024-1766, Los Angeles, California
    Arthur Peskoff
  2. Cardiovascular Research Laboratory, Departments of Physiology and Medicine, University of California at Los Angeles School of Medicine, 90024-1760, Los Angeles, California
    Jan A. Posit & Glenn A. Langer

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  1. Arthur Peskoff
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  2. Jan A. Posit
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  3. Glenn A. Langer
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Peskoff, A., Posit, J.A. & Langer, G.A. Sarcolemmal calcium binding sites in heart: II. Mathematical model for diffusion of calcium released from the sarcoplasmic reticulum into the diadic region.J. Membarin Biol. 129, 59–69 (1992). https://doi.org/10.1007/BF00232055

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