Ion transporters in secretory and cyclically modulating ameloblasts: a new hypothesis for cellular control of preeruptive enamel maturation

Am J Physiol Cell Physiol. 2010 Dec;299(6):C1299-307. doi: 10.1152/ajpcell.00218.2010. Epub 2010 Sep 15.


Mature enamel consists of densely packed and highly organized large hydroxyapatite crystals. The molecular machinery responsible for the formation of fully matured enamel is poorly described but appears to involve oscillative pH changes at the enamel surface. We conducted an immunohistochemical investigation of selected transporters and related proteins in the multilayered rat incisor enamel organ. Connexin 43 (Cx-43) is found in papillary cells and ameloblasts, whereas Na(+)-K(+)-ATPase is heavily expressed during maturation in the papillary cell layer only. Given the distribution of Cx-43 channels and Na(+)-K(+)-ATPase, we suggest that ameloblasts and the papillary cell layer act as a functional syncytium. During enamel maturation ameloblasts undergo repetitive cycles of modulation between ruffle-ended (RA) and smooth-ended (SA) ameloblast morphologies. Carbonic anhydrase II and vacuolar H(+)-ATPase are expressed simultaneously at the beginning of the maturation stage in RA cells. The proton pumps are present in the ruffled border of RA and appear to be internalized during the SA stage. Both papillary cells and ameloblasts express plasma membrane acid/base transporters (AE2, NBC, and NHE1). AE2 and NHE1 change position relative to the enamel surface as localization of the tight junctions changes during ameloblast modulation cycles. We suggest that the concerted action of the papillary cell layer and the modulating ameloblasts regulates the enamel microenvironment, resulting in oscillating pH fluctuations. The pH fluctuations at the enamel surface may be required to keep intercrystalline spaces open in the surface layers of the enamel, enabling degraded enamel matrix proteins to be removed while hydroxyapatite crystals grow as a result of influx of calcium and phosphate ions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ameloblasts / cytology
  • Ameloblasts / enzymology*
  • Amelogenesis*
  • Animals
  • Anion Transport Proteins / metabolism
  • Antiporters / metabolism
  • Carbonic Anhydrase II / metabolism
  • Connexin 43 / metabolism
  • Dental Enamel / enzymology*
  • Hydrogen-Ion Concentration
  • Ion Transport
  • Male
  • Proton Pumps / metabolism
  • Rats
  • Rats, Wistar
  • SLC4A Proteins
  • Sodium-Hydrogen Exchanger 1
  • Sodium-Hydrogen Exchangers / metabolism
  • Sodium-Potassium-Exchanging ATPase / metabolism
  • Vacuolar Proton-Translocating ATPases / metabolism


  • Anion Transport Proteins
  • Antiporters
  • Connexin 43
  • Proton Pumps
  • SLC4A Proteins
  • Slc9a1 protein, rat
  • Sodium-Hydrogen Exchanger 1
  • Sodium-Hydrogen Exchangers
  • Vacuolar Proton-Translocating ATPases
  • Carbonic Anhydrase II
  • Sodium-Potassium-Exchanging ATPase