Numerical simulation of Ca2+ "sparks" in skeletal muscle

A three dimensional (3D) model of Ca2+ diffusion and binding within a sarco mere of a myofibril, including Ca2+ binding sites troponin, parvalbumin, sa rcoplasmic 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), calc ium dye (CaD), and Ca2+ were included in the model. The Ca2+ release curren t was assumed to last 8 ms, to arise within 4 x 10(-5) mu m(3) 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 distribut ion of CaD with a Gaussian kernel approximating the point spread function o f the microscope. Our results indicate that the amplitude of the simulated spark is proportional to the Ca2+ release current if all other model parame ters 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 si mulated sparks exhibited similar amplitudes and temporal properties, but le ss spatial spread than experimentally observed sparks.