Calcium Transport in Specialized Dental Epithelia and Its Modulation by Fluoride

Most cells use calcium (Ca²⁺) as a second messenger to convey signals that affect a multitude of biological processes. The ability of Ca²⁺ to bind to proteins to alter their charge and conformation is essential to achieve its signaling role. Cytosolic Ca²⁺ (_cCa²⁺) concentration is maintained low at ~100 nM so that the impact of elevations in _cCa²⁺ is readily sensed and transduced by cells. However, such elevations in _cCa²⁺ must be transient to prevent detrimental effects. Cells have developed a variety of systems to rapidly clear the excess of _cCa²⁺ including Ca²⁺ pumps, exchangers and sequestering Ca²⁺ within intracellular organelles. This Ca²⁺ signaling toolkit is evolutionarily adapted so that each cell, tissue, and organ can fulfill its biological function optimally. One of the most specialized cells in mammals are the enamel forming cells, the ameloblasts, which also handle large quantities of Ca²⁺. The end goal of ameloblasts is to synthesize, secrete and mineralize a unique proteinaceous matrix without the benefit of remodeling or repair mechanisms. Ca²⁺ uptake into ameloblasts is mainly regulated by the store operated Ca²⁺ entry (SOCE) before it is transported across the polarized ameloblasts to reach the insulated enamel space. Here we review the ameloblasts Ca²⁺ signaling toolkit and address how the common electronegative non-metal fluoride can alter its function, potentially addressing the biology of dental fluorosis.