The interstitial cells of Cajal (ICC) drive rhythmic pacemaking contractions in the gastro-intestinal system. The ICC generate pacemaking signals by membrane depolarizations associated with the release of intracellular calcium (Ca²⁺) in the endoplasmic reticulum (ER) through inositol-trisphosphate (IP₃) receptors (IP₃R) and uptake by mitochondria (MT). This Ca²⁺ dynamic is hypothesized to generate pacemaking signals by calibrating ER Ca²⁺ store depletions and membrane depolarization with ER store operated Ca²⁺ entry (SOCE) mechanisms. Using a biophysically based spatio-temporal model of integrated Ca²⁺ transport in the ICC, we determine the feasibility of ER depletion timescale correspondence with experimentally observed pacemaking frequencies while considering the impact of IP₃R Ca²⁺ release and MT uptake on bulk cytosolic Ca²⁺ levels, since persistent elevations of free intracellular Ca²⁺ are toxic to the cell. MT densities and distributions are varied in the model geometry to observe MT influence on free cytosolic Ca²⁺ and the resulting frequencies of ER Ca²⁺ store depletions, and the sarco-endoplasmic reticulum Ca²⁺ ATP-ase (SERCA) and IP3 agonist concentrations are also varied. Our simulations show high MT densities observed in the ICC are more relevant to ER establishing Ca²⁺ depletion frequencies than protection of the cytosol from elevated free Ca²⁺, while the SERCA pump is more relevant to containing cytosolic Ca²⁺ elevations. Our results further suggest that the level of IP₃ agonist stimulating ER Ca²⁺ release, subsequent MT uptake and eventual activation of ER store-operated Ca²⁺ entry may determine frequencies of rhythmic pacemaking exhibited by the ICC across species and tissue types.