The dynamics of Ca within the sarcoplasmic reticulum of frog skeletal muscle. A simulation study.

In skeletal muscle, Ca release from the sarcoplasmic reticulum (SR) triggers contraction. In this study we develop a two compartment model to account for the Ca dynamics in frog skeletal muscle fibers. The two compartments in the model correspond to the SR and the cytoplasm, where the myofibrils are placed. We use a detailed model for the several Ca binding proteins in the cytoplasm in line with previous models. As a new feature, Ca binding sites within the SR, attributed to calsequestrin, are modeled based on experimentally obtained properties. The intra SR Ca buffer shows cooperativity, well represented by a Hill equation with parameters that depend on the initial [Ca] in the SR ([Ca]). The number of total sites as well as the [Ca] of half saturation are reduced as the resting [Ca] is reduced, on the other hand the Hill number is not changed. The buffer power remained roughly constant. The release process is activated by a voltage dependent mechanism that increases the Ca permeability of the SR. We use the permeability time course and amplitude experimentally obtained during a voltage clamp pulse to drive the simulations. This model successfully reproduces the SR and cytoplasmic transients observed. Additionally, we simulate [Ca] transients in the case of high concentration of extrinsic Ca buffers added to the cytoplasm to explore what properties of the permeability are necessary to account for the experimentally observed [Ca] transients. The main novelty of the model, the intra SR Ca buffer, is crucial for reproducing the experimental observations and it would be of use in future theoretical studies of excitation contraction coupling in skeletal muscle.