Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China.
Basic Res Cardiol. 2012 Sep;107(5):282. doi: 10.1007/s00395-012-0282-4. Epub 2012 Jul 18.
Transient receptor potential melastatin-7 (TRPM7) channels have been recently reported in human atrial fibroblasts and are believed to mediate fibrogenesis in human atrial fibrillation. The present study investigates whether TRPM7 channels are expressed in human atrial myocytes using whole-cell patch voltage-clamp, RT-PCR and Western blotting analysis. It was found that a gradually activated TRPM7-like current was recorded with a K(+)- and Mg(2+)-free pipette solution in human atrial myocytes. The current was enhanced by removing extracellular Ca(2+) and Mg(2+), and the current increase could be inhibited by Ni(2+) or Ba(2+). The TRPM7-like current was potentiated by acidic pH and inhibited by La(3+) and 2-aminoethoxydiphenyl borate. In addition, Ca(2+)-activated TRPM4-like current was recorded in human atrial myocytes with the addition of the Ca(2+) ionophore A23187 in bath solution. RT-PCR and Western immunoblot analysis revealed that in addition to TRPM4, TRPM7 channel current, mRNA and protein expression were evident in human atrial myocytes. Interestingly, TRPM7 channel protein, but not TRPM4 channel protein, was significantly increased in human atrial specimens from the patients with atrial fibrillation. Our results demonstrate for the first time that functional TRPM7 channels are present in human atrial myocytes, and the channel expression is upregulated in the atria with atrial fibrillation.
瞬时受体电位 melastatin-7（TRPM7）通道最近在人心房成纤维细胞中被报道，并被认为介导人心房颤动中的纤维化。本研究使用全细胞膜片钳电压钳、RT-PCR 和 Western 印迹分析来研究 TRPM7 通道是否在人心房心肌细胞中表达。结果发现，在人心房心肌细胞中，用不含 K+和 Mg2+的 pipette 溶液记录到逐渐激活的 TRPM7 样电流。该电流在外液去除 Ca2+和 Mg2+时增强，并且电流增加可被 Ni2+或 Ba2+抑制。TRPM7 样电流被酸性 pH 增强，并被 La3+和 2-氨基乙氧基二苯硼酸盐抑制。此外，在 bath 溶液中加入 Ca2+离子载体 A23187，可在人心房心肌细胞中记录到 Ca2+激活的 TRPM4 样电流。RT-PCR 和 Western 免疫印迹分析显示，除了 TRPM4 之外，人心房心肌细胞中还存在 TRPM7 通道电流、mRNA 和蛋白表达。有趣的是，在患有心房颤动的人心房标本中，TRPM7 通道蛋白而非 TRPM4 通道蛋白的表达显著增加。我们的结果首次表明，功能性 TRPM7 通道存在于人心房心肌细胞中，并且在心房颤动的心房中，该通道的表达上调。
