Physiological Institute, University of Regensburg, University street 31, D-93053, Regensburg, Germany.
Pflugers Arch. 2023 Aug;475(8):995-1007. doi: 10.1007/s00424-023-02829-5. Epub 2023 Jul 13.
The TMEM16A (ANO1) Cl channel is activated by Ca in a voltage-dependent manner. It is broadly expressed and was shown to be also present in renal proximal tubule (RPT). KCNQ1 is an entirely different K selective channel that forms the cardiac I potassium channel together with its ß-subunit KCNE1. Surprisingly, KCNE1 has been claimed to interact with TMEM16A, and to be required for activation of TMEM16A in mouse RPT. Interaction with KCNE1 was reported to switch TMEM16A from a Ca2-dependent to a voltage-dependent ion channel. Here we demonstrate that KCNE1 is not expressed in mouse RPT. TMEM16A expressed in RPT is activated by angiotensin II and ATP in a KCNE1-independent manner. Coexpression of KCNE1 does not change TMEM16A to a voltage gated Cl channel and Ca-dependent regulation of TMEM16A is fully maintained in the presence of KCNE1. While overexpressed KCNE1 slightly affects Ca-dependent regulation of TMEM16A, the data provide no evidence for KCNE1 being an auxiliary functional subunit for TMEM16A.
TMEM16A（ANO1）氯离子通道可被 Ca2+ 以电压依赖的方式激活。它广泛表达，并被证明也存在于肾脏近端小管（RPT）中。KCNQ1 是一种完全不同的 K 选择性通道，与其β亚基 KCNE1 一起构成心脏 I 钾通道。令人惊讶的是，有人声称 KCNE1 与 TMEM16A 相互作用，并对激活鼠 RPT 中的 TMEM16A 是必需的。与 KCNE1 的相互作用据报道将 TMEM16A 从 Ca2+ 依赖性离子通道转换为电压依赖性离子通道。在这里，我们证明 KCNE1 不在鼠 RPT 中表达。在 RPT 中表达的 TMEM16A 被血管紧张素 II 和 ATP 以 KCNE1 独立的方式激活。KCNE1 的共表达不会将 TMEM16A 转变为电压门控 Cl 通道，并且在存在 KCNE1 的情况下，TMEM16A 的 Ca2+依赖性调节得到完全维持。虽然过表达的 KCNE1 会轻微影响 TMEM16A 的 Ca2+依赖性调节，但这些数据没有提供 KCNE1 是 TMEM16A 的辅助功能亚基的证据。
