Sarcolemmal calcium binding sites in heart: II. Mathematical model for diffusion of calcium released from the sarcoplasmic reticulum into the diadic region.
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 approximately 1.5 mM in 20-msec and then falls to approximately 0.1 microM in less than 3 msec. Adding binding sites reduces peak [Ca] to approximately 0.6 mM but prolongs its decline, requiring approximately 200 msec to reach 20 microM. For repetitive release [Ca] is greater than 100 microM 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 Na-Ca exchanger (Km(Ca) approximately 20 microM) to continue at a significant level for greater than 200 msec. (ii) The time constant for inactivation of release from the "feet" must be much greater than for activation if Ca-induced Ca release is to continue for greater than 1-2 msec.
Peskoff
A
A
Department of Biomathematics, University of California, Los Angeles School of Medicine 90024-1766.
Post
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JA
Langer
G A
GA
D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism*; D008962:Models, Theoretical; D009206:Myocardium / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D012508:Sarcolemma / Q000378:metabolism* / Q000648:ultrastructure; D012519:Sarcoplasmic Reticulum / Q000378:metabolism* / Q000648:ultrastructure
D002118:Calcium