TRPM7-Mediated Calcium Transport in HAT-7 Ameloblasts.

TRPM7-Mediated Calcium Transport in HAT-7 Ameloblasts.
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TRPM7介导的HAT-7成成木细胞中的钙转运。

DOI:
10.3390/ijms22083992
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发表时间:
2021-04-13
影响因子:
5.6
通讯作者:
Zsembery Á
Zsembery Á
中科院分区:
生物学2区
文献类型:
--
作者:
Kádár K;Juhász V;Földes A;Rácz R;Zhang Y;Löchli H;Kató E;Köles L;Steward MC;DenBesten P;Varga G;Zsembery Á

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TRPM7在细胞内Ca2+、Zn2+和Mg2+的稳态中起重要作用。TRPM7通道在成釉细胞中大量表达,在缺乏TRPM7时,牙釉质矿化不良。在HAT - 7大鼠成釉细胞系中研究了TRPM7通道在釉质形成过程中Ca2+转运的潜在作用。这些细胞显示出强烈的TRPM7 mRNA和蛋白质表达。观察到了特征性的TRPM7跨膜电流,在细胞内无Mg2+([Mg2+]i)时该电流增加,[Mg2+]i升高时电流降低,并且被TRPM7抑制剂NS8593和FTY720抑制。米贝拉地尔诱发了类似的电流,该电流被升高的[Mg2+]i抑制,降低细胞外pH刺激跨膜电流,该电流被FTY720抑制。纳曲本和米贝拉地尔都诱发了Ca2+内流,酸性细胞内环境进一步增强了这种内流。钙库操纵性钙内流(SOCE)抑制剂BTP2阻断了由纳曲本诱导的Ca2+进入,但不阻断由米贝拉地尔诱导的Ca2+进入。因此,在HAT - 7细胞中,TRPM7既可能作为Orai依赖性Ca2+摄取的潜在调节剂,又可能作为对pH敏感的独立Ca2+进入途径。因此,TRPM7可能直接有助于釉质形成过程中的跨上皮Ca2+转运。
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.
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