Abstract
A three dimensional (3D) model of Ca 2+ diffusion and binding within a sarcomere of a myofibril, including Ca 2+ binding sites troponin, parvalbumin, sarcoplasmic reticulum Ca 2+ pump, and fluorescent Ca 2+-indicator dye (fluo-3), was developed to numerically simulate laser scanning confocal microscope images of Ca 2+ “sparks” in skeletal muscle. Diffusion of free dye (D), calcium dye (CaD), and Ca 2+ were included in the model. The Ca 2+ release current was assumed to last 8 ms, to arise within 4 × 10 −5 μm 3 at the triad and to be constant during release. Line scan confocal fluorescence images of Ca 2+ 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 Ca 2+ 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 Ca 2+ all have significant effects on the simulated Ca 2+ sparks. The simulated sparks exhibited similar amplitudes and temporal properties, but less spatial spread than experimentally observed sparks.
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