Sarcolemmal calcium binding sites in heart: II. Mathematical model for diffusion of calcium released from the sarcoplasmic reticulum into the diadic region |
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Authors: | Arthur Peskoff Jan A Posit Glenn A Langer |
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Institution: | (1) Departments of Biomathematics and Physiology, University of California at Los Angeles School of Medicine, 90024-1766 Los Angeles, California;(2) Cardiovascular Research Laboratory, Departments of Physiology and Medicine, University of California at Los Angeles School of Medicine, 90024-1760 Los Angeles, California;(3) Present address: Institute of Biomembranes, State University Utrecht, 3584 Utrecht, CH, The Netherlands |
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Abstract: | 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 m in < 3 msec. Adding binding sites reduces peak Ca] to 0.6 mm but prolongs its decline, requiring 200 msec to reach 20 m. For repetitive release Ca] is > 100 m 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 m) 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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Keywords: | diffusion model subsarcolemmal space calcium diffusion calcium exchange calcium binding excitationcontraction coupling |
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