In whole-cell patch clamp recordings, it was discovered that normal human adrenal zona glomerulosa (AZG) cells express members of the three major families of K⁺ channels. Among these are a two pore (K2P) leak-type and a G-protein-coupled, inwardly-rectifying (GIRK) channel, both inhibited by peptide hormones that stimulate aldosterone secretion. The K2P current displayed properties identifying it as TREK-1 (KCNK2). This outwardly-rectifying current was activated by arachidonic acid and inhibited by angiotensin II (AngII), adrenocorticotrophic hormone (ACTH), and forskolin. The activation and inhibition of TREK-1 was coupled to AZG cell hyperpolarization and depolarization, respectively. A second K2P channel, TASK-1 (KCNK3), was expressed at a lower density in AZG cells. Human AZG cells also express inwardly rectifying K⁺ current(s) (K_IR) that include quasi-instantaneous and time-dependent components. This is the first report demonstrating the presence of K_IR in whole cell recordings from AZG cells of any species. The time-dependent current was selectively inhibited by AngII, and ACTH, identifying it as a G protein-coupled (GIRK) channel, most likely K_IR3.4 (KCNJ5). The quasi-instantaneous K_IR current was not inhibited by AngII or ACTH, and may be a separate non-GIRK current. Finally, AZG cells express a voltage-gated, rapidly inactivating K⁺ current whose properties identified as K_V1.4 (KCNA4), a conclusion confirmed by Northern blot. These findings demonstrate that human AZG cells express K2P and GIRK channels whose inhibition by AngII and ACTH are likely coupled to depolarization-dependent secretion. They further demonstrate that human AZG K⁺ channels differ fundamentally from the widely adopted rodent models for human aldosterone secretion.

中文翻译：

---

人肾上腺肾小球细胞表达受 AngII 和 ACTH 抑制的 K2P 和 GIRK 钾通道

在全细胞膜片钳记录中，发现正常人肾上腺肾小球带 (AZG) 细胞表达 K ^{+三个主要家族的成员}渠道。其中包括双孔 (K2P) 泄漏型和 G 蛋白偶联的内向整流 (GIRK) 通道，两者都被刺激醛固酮分泌的肽激素抑制。K2P 当前显示的属性将其标识为 TREK-1 (KCNK2)。这种向外整流的电流被花生四烯酸激活并被血管紧张素 II (AngII)、促肾上腺皮质激素 (ACTH) 和毛喉素抑制。TREK-1 的激活和抑制分别与 AZG 细胞超极化和去极化相关联。第二个 K2P 通道，TASK-1 (KCNK3)，在 AZG 细胞中以较低的密度表达。人 AZG 细胞也表达向内整流的 K ⁺电流 (K _IR) 包括准瞬时和时间相关的分量。这是第一份证明在来自任何物种的 AZG 细胞的全细胞记录中存在 K _{IR的报告。}时间依赖性电流被 AngII 和 ACTH 选择性抑制，将其识别为 G 蛋白偶联 (GIRK) 通道，最有可能是 K _IR 3.4 (KCNJ5)。准瞬时 K _IR电流不受 AngII 或 ACTH 抑制，可能是单独的非 GIRK 电流。最后，AZG 细胞表达一种电压门控的、快速失活的 K ⁺电流，其特性被识别为 K _V1.4（KCNA4），Northern印迹证实的结论。这些发现表明，人 AZG 细胞表达 K2P 和 GIRK 通道，其受 AngII 和 ACTH 的抑制可能与去极化依赖性分泌有关。他们进一步证明，人类 AZG K ⁺通道与广泛采用的人类醛固酮分泌啮齿动物模型根本不同。