Finite element analysis predicts Ca microdomains within tubular-sarcoplasmic reticular junctions of amphibian skeletal muscle.

A finite element analysis modelled diffusional generation of steady-state Ca microdomains within skeletal muscle transverse (T)-tubular-sarcoplasmic reticular (SR) junctions, sites of ryanodine receptor (RyR)-mediated SR Ca release. It used established quantifications of sarcomere and T-SR anatomy (radial diameter [Formula: see text]; axial distance [Formula: see text]). Its boundary SR Ca influx densities,[Formula: see text], reflected step impositions of influxes, [Formula: see text] deduced from previously measured Ca signals following muscle fibre depolarization. Predicted steady-state T-SR junctional edge [Ca], [Ca] matched reported corresponding experimental cytosolic [Ca] elevations given diffusional boundary efflux [Formula: see text] established cytosolic Ca diffusion coefficients [Formula: see text] and exit length [Formula: see text]. Dependences of predicted [Ca] upon [Formula: see text] then matched those of experimental [Ca] upon Ca release through their entire test voltage range. The resulting model consistently predicted elevated steady-state T-SR junctional ~ µM-[Ca] elevations radially declining from maxima at the T-SR junction centre along the entire axial T-SR distance. These [Ca] heterogeneities persisted through 10- and fivefold, variations in D and w around, and fivefold reductions in d below, control values, and through reported resting muscle cytosolic [Ca] values, whilst preserving the flux conservation ([Formula: see text] condition, [Formula: see text]. Skeletal muscle thus potentially forms physiologically significant ~ µM-[Ca] T-SR microdomains that could regulate cytosolic and membrane signalling molecules including calmodulin and RyR, These findings directly fulfil recent experimental predictions invoking such Ca microdomains in observed regulatory effects upon Na channel function, in a mechanism potentially occurring in similar restricted intracellular spaces in other cell types.