Calcium dynamics in small spaces: Lessons learned from modeling in dendritic spines

Spatiotemporal dynamics of calcium regulation in subcellular regions is critical for precise local control of cell signaling. Recent studies have shown that, in addition to biochemical control of localized calcium signaling through buffers and channels, the geometry of the small spaces in which calcium signaling occurs also matters. Geometric organization becomes particularly important when considering the role of organelles such as the mitochondria and endoplasmic reticulum in regulating calcium signaling. Here, we discuss recent advances in our understanding of calcium dynamics in small spaces such as dendritic spines and how computational modeling can reveal a complex interplay between geometry and receptor clustering. We close with other biological examples where such interactions may be important and suggest the possibility of generalizable biophysical principles of localized calcium control.