Activation of mouse Otop3 proton channels by Zn2+
Activation of mouse Otop3 proton channels by Zn2+
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Zn2 激活小鼠 Otop3 质子通道
DOI：
10.1016/j.bbrc.2023.03.066
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发表时间：
2023
影响因子：
3.1
通讯作者：
Sakai Hideki
中科院分区：
文献类型：
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作者：
Fujii Takuto;Shimizu Takahiro;Kaji Yukino;Katoh Mizuki;Sakai Hideki
Otopetrins（Otop 1-Otop 3）是一个新发现的由细胞外酸化激活的质子（H+）通道家族。在这里，我们发现，Zn 2+激活小鼠Otop 3（mOtop 3）质子通道，通过使用电生理膜片钳技术。在表达mOtop 3的人胚肾HEK 293 T细胞中，在pH 5.0的细胞外酸化后观察到双相内向mOtop 3 H+电流，包括快速瞬时电流，随后是持续电流。在pH 6.5和7.4下没有观察到mOtop 3通道的显著激活，但有趣的是，在这些pH条件下，Zn 2+剂量依赖性地诱导mOtop 3的持续激活。增加Zn 2+浓度对通道电流的反转电位没有影响，表明Zn 2+不渗透通过mOtop 3。在二价金属阳离子中，mOtop 3通道的激活对Zn 2+是特异性的。我们的研究结果揭示了一种新的调制机制mOtop 3质子通道的Zn 2+。
Otopetrins (Otop1-Otop3) belong to a newly identified family of proton (H+) channels activated by extracellular acidification. Here, we found that Zn2+activates the mouse Otop3 (mOtop3) proton channels by using electrophysiological patch-clamp techniques. In mOtop3-expressing human embryonic kidney HEK293T cells, a biphasic inward mOtop3 H+current comprising a fast transient current followed by a sustained current was observed upon extracellular acidification at pH 5.0. No significant activation of the mOtop3 channel was observed at pH 6.5 and 7.4, but interestingly, Zn2+dose-dependently induced a sustained activation of mOtop3 under these pH conditions. Increasing the Zn2+concentration had no effect on the reversal potential of the channel currents, suggesting that Zn2+does not permeate through the mOtop3. The activation of the mOtop3 channel was specific to Zn2+among divalent metal cations. Our findings reveal a novel modulatory mechanism of mOtop3 proton channels by Zn2+.