Evidence that calcium entry into calcium-transporting dental enamel cells is regulated by cholecystokinin, acetylcholine and ATP

Meerim K. Nurbaeva, Miriam Eckstein, Arun Devotta, Jean Pierre Saint-Jeannet, David I. Yule, Michael J. Hubbard, Rodrigo S. Lacruz

Research output: Contribution to journalArticlepeer-review


Dental enamel is formed by specialized epithelial cells which handle large quantities of Ca2+ while producing the most highly mineralized tissue. However, the mechanisms used by enamel cells to handle bulk Ca2+ safely remain unclear. Our previous work contradicted the dogma that Ca2+ is ferried through the cytosol of Ca2+-transporting cells and instead suggested an organelle-based route across enamel cells. This new paradigm involves endoplasmic reticulum (ER)-associated Ca2+ stores and their concomitant refilling by store-operated Ca2+ entry (SOCE) mediated by Ca2+ release activated Ca2+ (CRAC) channels. Given that Ca2+ handling is maximal during the enamel-mineralization stage (maturation), we anticipated that SOCE would also be elevated then. Confirmation was obtained here using single-cell recordings of cytosolic Ca2+ concentration ([Ca2+]cyt) in rat ameloblasts. A candidate SOCE agonist, cholecystokinin (CCK), was found to be upregulated during maturation, with Cck transcript abundance reaching 30% of that in brain. CCK-receptor transcripts were also detected and Ca2+ imaging showed that CCK stimulation increased [Ca2+]cyt in a dose-responsive manner that was sensitive to CRAC-channel inhibitors. Similar effects were observed with two other SOCE activators, acetylcholine and ATP, whose receptors were also found in enamel cells. These results provide the first evidence of a potential regulatory system for SOCE in enamel cells and so strengthen the Ca2+ transcytosis paradigm for ER-based transport of bulk Ca2+. Our findings also implicate enamel cells as a new physiological target of CCK and raise the possibility of an auto/paracrine system for regulating Ca2+ transport.

Original languageEnglish (US)
Article number801
JournalFrontiers in Physiology
Issue numberJUL
StatePublished - Jul 2 2018


  • ACh
  • ATP
  • Ameloblasts
  • CCK
  • CRAC channels
  • Ca
  • SOCE

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)


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