Kolesnikov D O, Grigorieva E R, Nomerovskaya M A, Reshetin D S, Shalygin A V, Kaznacheyeva E V
Institute of Cytology of the Russian Academy of Sciences, St. Petersburg, 194064 Russian Federation.
Acta Naturae. 2024 Jan-Mar;16(1):40-47. doi: 10.32607/actanaturae.27338.
Proteins belonging to the anoctamin (ANO) family form calcium-activated chloride channels (CaCCs). The most unusual member of this family, ANO6 (TMEM16F), simultaneously exhibits the functions of calcium-dependent scramblase and the ion channel. ANO6 affects the plasma membrane dynamics and phosphatidylserine transport; it is also involved in programmed cell death. The properties of ANO6 channels remain the subject of debate. In this study, we investigated the effect of variations in the intracellular and extracellular concentrations of calcium ions on the electrophysiological properties of endogenous ANO6 channels by recording single ANO6 channels. It has been demonstrated that (1) a high calcium concentration in an extracellular solution increases the activity of endogenous ANO6 channels, (2) the permeability of endogenous ANO6 channels for chloride ions is independent of the extracellular concentration of calcium ions, (3) that an increase in the intracellular calcium concentration leads to the activation of endogenous ANO6 channels with double amplitude, and (4) that the kinetics of the channel depend on the plasma membrane potential rather than the intracellular concentration of calcium ions. Our findings give grounds for proposing new mechanisms for the regulation of the ANO6 channel activity by calcium ions both at the inner and outer sides of the membrane.
属于 anoctamin（ANO）家族的蛋白质形成钙激活氯离子通道（CaCCs）。该家族最特别的成员 ANO6（TMEM16F）同时具有钙依赖性磷脂翻转酶和离子通道的功能。ANO6 影响质膜动力学和磷脂酰丝氨酸转运；它还参与程序性细胞死亡。ANO6 通道的特性仍是一个有争议的话题。在本研究中，我们通过记录单个 ANO6 通道，研究了细胞内和细胞外钙离子浓度变化对内源性 ANO6 通道电生理特性的影响。结果表明：（1）细胞外溶液中的高钙浓度会增加内源性 ANO6 通道的活性；（2）内源性 ANO6 通道对氯离子的通透性与细胞外钙离子浓度无关；（3）细胞内钙浓度的增加会导致内源性 ANO6 通道的活性加倍；（4）通道的动力学取决于质膜电位，而非细胞内钙离子浓度。我们的研究结果为提出钙离子在膜内侧和外侧调节 ANO6 通道活性的新机制提供了依据。
