UC San Diego

Ca2+ signaling within myofibers is fundamental for muscle contraction facilitating activities from everyday tasks to high-intensity exercise. Stimulation at the neuromuscular junction induces an action potential that propagates along and throughout the myofiber, leading to release of Ca2+ from the sarcoplasmic reticulum (SR). Ca2+ then binds to troponin, enabling muscle contraction. Recent research highlights the role of store-operated calcium entry (SOCE) in maintaining intracellular Ca2+ stores during muscle activation. Upon SR Ca2+ depletion, stromal interaction molecule 1 in the SR membrane forms assemblies with ORAI1 channels in the sarcolemma, facilitating Ca2+ influx into myoplasm that can then be transported back into the SR. In this thesis, we develop a multi-compartment model to capture the role of SOCE in myoplasmic Ca2+ dynamics and force production during exercise. This model builds on previous models in the literature, integrating features of Ca2+ signaling and APs by including a novel combination of relevant ion channels and pumps, as well as Ca2+ buffers, and SOCE. Model parameters were calibrated against experimental data to ensure physiological relevance and model robustness. The model was simulated at various frequencies and durations of stimuli relevant to endurance vs resistance exercises. The model predicted reductions in both the maximum and average myoplasmic Ca2+ in the absence of SOCE flux, implying a diminished ability to sustain high force. The strength of this effect varied according to the frequency and exercise type. This study offers insights into muscle performance, endurance, and recovery, relevant to athletic training, physical therapy, and medical research.