Center of Physiology, Pathophysiology and Biophysics, Paracelsus Medical University, Nuremberg, Germany.
Department of Physiology & Biophysics, Rush University, Chicago, IL, USA.
FEBS J. 2023 Feb;290(4):1008-1026. doi: 10.1111/febs.16617. Epub 2022 Sep 20.
Voltage-gated ion channels, whose first identified function was to generate action potentials, are divided into subfamilies with numerous members. The family of voltage-gated proton channels (H ) is tiny. To date, all species found to express H have exclusively one gene that codes for this unique ion channel. Here we report the discovery and characterization of three proton channel genes in the classical model system of neural plasticity, Aplysia californica. The three channels (AcH 1, AcH 2, and AcH 3) are distributed throughout the whole animal. Patch-clamp analysis confirmed proton selectivity of these channels but they all differed markedly in gating. AcH 1 gating resembled H in mammalian cells where it is responsible for proton extrusion and charge compensation. AcH 2 activates more negatively and conducts extensive inward proton current, properties likely to acidify the cytosol. AcH 3, which differs from AcH 1 and AcH 2 in lacking the first arginine in the S4 helix, exhibits proton selective leak currents and weak voltage dependence. We report the expansion of the proton channel family, demonstrating for the first time the expression of three functionally distinct proton channels in a single species.
电压门控离子通道，其最初被确定的功能是产生动作电位，分为具有众多成员的亚家族。电压门控质子通道（H）家族很小。迄今为止，所有被发现表达 H 的物种都仅有一种基因编码这种独特的离子通道。在这里，我们报告了在经典的神经可塑性模型系统——加利福尼亚海兔中发现和表征的三种质子通道基因。这三种通道（AcH1、AcH2 和 AcH3）分布在整个动物体内。膜片钳分析证实了这些通道的质子选择性，但它们在门控方面有明显的差异。AcH1 的门控类似于哺乳动物细胞中的 H，它负责质子外排和电荷补偿。AcH2 更负地激活，并传导广泛的内向质子电流，这些特性可能使细胞质酸化。AcH3 与 AcH1 和 AcH2 不同，它缺少 S4 螺旋中的第一个精氨酸，表现出质子选择性泄漏电流和弱电压依赖性。我们报告了质子通道家族的扩展，首次证明了在单个物种中表达三种功能不同的质子通道。
