TRPM7-Mediated Calcium Transport in HAT-7 Ameloblasts

TRPM7 plays an important role in cellular Ca(2+), Zn(2+) and Mg(2+) 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 Ca(2+) 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 Mg(2+) ([Mg(2+)](i)), were reduced by elevated [Mg(2+)](i), and were inhibited by the TRPM7 inhibitors NS8593 and FTY720. Mibefradil evoked similar currents, which were suppressed by elevated [Mg(2+)](i), reducing extracellular pH stimulated transmembrane currents, which were inhibited by FTY720. Naltriben and mibefradil both evoked Ca(2+) influx, which was further enhanced by the acidic intracellular conditions. The SOCE inhibitor BTP2 blocked Ca(2+) entry induced by naltriben but not by mibefradil. Thus, in HAT-7 cells, TRPM7 may serves both as a potential modulator of Orai-dependent Ca(2+) uptake and as an independent Ca(2+) entry pathway sensitive to pH. Therefore, TRPM7 may contribute directly to transepithelial Ca(2+) transport in amelogenesis.