TRPM7 is a cation channel-protein kinase highly expressed in T lymphocytes and other immune cells. It has been proposed to constitute a cellular entry pathway for Mg²⁺ and divalent metal cations such as Ca²⁺, Zn²⁺, Cd²⁺, Mn²⁺, and Ni²⁺. TRPM7 channels are inhibited by cytosolic Mg²⁺, rendering them largely inactive in intact cells. The dependence of channel activity on extracellular Mg²⁺ is less well studied. Here, we measured native TRPM7 channel activity in Jurkat T cells maintained in external Mg²⁺ concentrations varying between 400 nM and 1.4 mM for 1–3 days, obtaining an IC₅₀ value of 54 μM. Maintaining the cells in 400 nM or 8 μM [Mg²⁺]_o resulted in almost complete activation of TRPM7 in intact cells, due to cytosolic Mg²⁺ depletion. A total of 1.4 mM [Mg²⁺]_o was sufficient to fully eliminate the basal current. Submillimolar concentrations of amiloride prevented cellular Mg²⁺ depletion but not loading. We investigated whether the cytotoxicity of TRPM7 permeant metal ions Ni²⁺, Zn²⁺, Cd²⁺, Co²⁺, Mn²⁺, Sr²⁺, and Ba²⁺ requires TRPM7 channel activity. Mg²⁺ loading modestly reduced cytotoxicity of Zn²⁺, Co²⁺, Ni²⁺, and Mn²⁺ but not of Cd²⁺. Channel blocker NS8593 reduced Co²⁺ and Mn²⁺ but not Cd²⁺ or Zn²⁺ cytotoxicity and interfered with Mg²⁺ loading as evaluated by TRPM7 channel basal activity. Ba²⁺ and Sr²⁺ were neither detectably toxic nor permeant through the plasma membrane. These results indicate that in Jurkat T cells, entry of toxic divalent metal cations primarily occurs through pathways distinct from TRPM7. By contrast, we found evidence that Mg²⁺ entry requires TRPM7 channels.

TRPM7 是一种阳离子通道蛋白激酶，在 T 淋巴细胞和其他免疫细胞中高度表达。已经提出为Mg ²⁺和二价金属阳离子如Ca ²⁺、Zn ²⁺、Cd ²⁺、Mn ²⁺和Ni ²⁺构成细胞进入途径。TRPM7 通道受到胞质 Mg ^{2+ 的}抑制，使它们在完整细胞中基本失活。通道活性对细胞外 Mg ²⁺的依赖性研究较少。在这里，我们测量了维持在外部 Mg ²⁺浓度在 400 nM 和 1.4 mM 之间变化 1-3 天的Jurkat T 细胞中的天然 TRPM7 通道活性，获得 IC ₅₀值 54 μM。将细胞维持在 400 nM 或 8 μM [Mg ²⁺ ] _o导致完整细胞中 TRPM7 几乎完全激活，这是由于细胞溶质 Mg ²⁺耗尽。总共 1.4 mM [Mg ²⁺ ] _o足以完全消除基础电流。亚毫摩尔浓度的阿米洛利可防止细胞中 Mg ²⁺消耗，但不能防止加载。我们研究了TRPM7 渗透金属离子Ni ²⁺、Zn ²⁺、Cd ²⁺、Co ²⁺、Mn ²⁺、Sr ²⁺和Ba ²⁺的细胞毒性是否需要TRPM7 通道活性。镁²⁺加载适度降低Zn ²⁺、Co ²⁺、Ni ²⁺和Mn ^{2+ 的}细胞毒性，但不降低Cd ^{2+ 的}细胞毒性。通道阻断剂 NS8593 降低 Co ²⁺和 Mn ²⁺但不降低 Cd ²⁺或 Zn ²⁺细胞毒性，并干扰 Mg ²⁺负载，如通过 TRPM7 通道基础活性评估。Ba ²⁺和Sr ²⁺既没有可检测的毒性也没有通过质膜渗透。这些结果表明，在 Jurkat T 细胞中，有毒二价金属阳离子的进入主要通过与 TRPM7 不同的途径发生。相比之下，我们发现证据表明 Mg ²⁺ 条目需要 TRPM7 通道。