Department of Neuroscience, Wright State University, Dayton, OH, USA.
Channels (Austin). 2012 Sep-Oct;6(5):362-9. doi: 10.4161/chan.21628. Epub 2012 Aug 24.
2-APB is a widely used compound in ion channel research. It affects numerous channels including inositol 1,4,5-trisphosphate receptors, store-operated calcium channels and TRP channels, TRPV3 and TRPM7 among them. A characteristic property of TRPM7 channels is their sensitivity to intracellular Mg ( 2+) and pH. Using patch clamp electrophysiology we find that in Jurkat T lymphocytes, 100-300 µM extracellular 2-APB reversibly inhibits TRPM7 channels when internal HEPES concentration is low (1 mM). Increasing the concentration to 140 mM abolishes the 2-APB effect. Using single-cell fluorescence pH video imaging, we show that at concentrations of 100 µM and higher, 2-APB potently acidifies the cytoplasm. We conclude that TRPM7 sensitivity to 2-APB is not direct but rather, can be explained by cytoplasmic acidification and a resulting channel inhibition.
2-APB 是离子通道研究中广泛使用的化合物。它影响许多通道，包括肌醇 1,4,5-三磷酸受体、储存操纵钙通道和 TRP 通道，其中包括 TRPV3 和 TRPM7。TRPM7 通道的一个特征性质是它们对细胞内镁（ 2+）和 pH 的敏感性。使用膜片钳电生理学，我们发现，在 Jurkat T 淋巴细胞中，当细胞内 HEPES 浓度较低（1mM）时，100-300µM 的细胞外 2-APB 可可逆抑制 TRPM7 通道。将浓度增加到 140mM 会消除 2-APB 的作用。使用单细胞荧光 pH 视频成像，我们表明，在 100µM 及更高浓度下，2-APB 强烈酸化细胞质。我们得出结论，TRPM7 对 2-APB 的敏感性不是直接的，而是可以通过细胞质酸化和由此产生的通道抑制来解释。
