Abstract
TRPM7 plays an important role in cellular Ca2+, Zn2+ and Mg2+ homeostasis. TRPM7 channels are abundantly expressed in ameloblasts and, in the absence of TRPM7, dental enamel is hypomineralized. The potential role of TRPM7 channels in Ca2+ transport during amelogenesis was investigated in the HAT-7 rat ameloblast cell line. The cells showed strong TRPM7 mRNA and protein expression. Characteristic TRPM7 transmembrane currents were observed, which increased in the absence of intracellular Mg2+ ([Mg2+]i), were reduced by elevated [Mg2+]i, and were inhibited by the TRPM7 inhibitors NS8593 and FTY720. Mibefradil evoked similar currents, which were suppressed by elevated [Mg2+]i, reducing extracellular pH stimulated transmembrane currents, which were inhibited by FTY720. Naltriben and mibefradil both evoked Ca2+ influx, which was further enhanced by the acidic intracellular conditions. The SOCE inhibitor BTP2 blocked Ca2+ entry induced by naltriben but not by mibefradil. Thus, in HAT-7 cells, TRPM7 may serves both as a potential modulator of Orai-dependent Ca2+ uptake and as an independent Ca2+ entry pathway sensitive to pH. Therefore, TRPM7 may contribute directly to transepithelial Ca2+ transport in amelogenesis.
Highlights
Ameloblasts are highly specialized epithelial cells with a key role in the mineralization of dental enamel
Quantitative gene expression analysis showed that TRPM7 mRNA was highly amplified in HAT-7 cells, relative to other amelogenesis-related ion transporters and channels, including NHE1, CFTR and pendrin (Figure 1A)
In this study we have shown that TRPM7 channels are expressed abundantly in HAT7 cells, both at mRNA and protein levels
Summary
Ameloblasts are highly specialized epithelial cells with a key role in the mineralization of dental enamel In this role, maturation ameloblasts mediate transepithelial secretion of Ca2+. Key to the function of maturation ameloblasts is their modulation of the acidity in the enamel-forming space, periodically cycling the extracellular pH between pH 6.2 and 7.2 while alternating between ruffle-ended and smooth-ended morphologies [1,3]. These pH changes are required both for the transport of dissolved Ca2+ and phosphate ions to the mineralization space, and for the subsequent precipitation of these ions into hydroxyapatite crystals. The large amount of calcium that must be transported to the highly mineralized enamel matrix suggests the possibility of additional mechanisms, such as calcium uptake via the divalent-cation-permeable
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