Biophys J, November 1999, p. 2333-2357, Vol. 77, No. 5

Numerical Simulation of Ca²⁺ "Sparks" in Skeletal Muscle

Yu-Hua Jiang,^* Michael G. Klein,^* and Martin F. Schneider^*

 ^*Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland 21201, and  Department of Mechanical Engineering, College of Engineering, University of Maryland Baltimore County, Baltimore, Maryland 21250, U.S.A.

A three dimensional (3D) model of Ca²⁺ diffusion and binding within a sarcomere of a myofibril, including Ca²⁺ binding sites troponin, parvalbumin, sarcoplasmic reticulum Ca²⁺ pump, and fluorescent Ca²⁺-indicator dye (fluo-3), was developed to numerically simulate laser scanning confocal microscope images of Ca²⁺ "sparks" in skeletal muscle. Diffusion of free dye (D), calcium dye (CaD), and Ca²⁺ were included in the model. The Ca²⁺ release current was assumed to last 8 ms, to arise within 4 × 10⁵ µm³ at the triad and to be constant during release. Line scan confocal fluorescence images of Ca²⁺ sparks were simulated by 3D convolution of the calculated distribution of CaD with a Gaussian kernel approximating the point spread function of the microscope. Our results indicate that the amplitude of the simulated spark is proportional to the Ca²⁺ release current if all other model parameters are constant. For a given release current, the kinetic properties and concentrations of the binding sites and the diffusion parameters of D, CaD, and Ca²⁺ all have significant effects on the simulated Ca²⁺ sparks. The simulated sparks exhibited similar amplitudes and temporal properties, but less spatial spread than experimentally observed sparks.

Biophys J, November 1999, p. 2333-2357, Vol. 77, No. 5
© 1999 by the Biophysical Society   0006-3495/99/11/2333/25  $2.00

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