TASK-5（KCNK15）属于双孔域钾（K2P）通道酸敏感亚家族，该亚家族包括TASK-1和TASK-3。 TASK-5 作为 K2P 通道脱颖而出，没有可用的功能数据，因为它在 2001 年被报告为非功能性的，因此“沉默”。在这里，我们证明 TASK-5 通道确实作为同二聚体没有功能，但参与与 TASK-1 和 TASK-3 功能性通道复合物的形成。 TASK-5负向调节TASK通道的表面表达，而位于质膜上的含有异聚TASK-5的通道复合物的特征是单通道电导的变化、Gq偶联受体介导的通道抑制和对TASK的敏感性调制器。 TASK-1/TASK-5异二聚体的独特药理学受到KCNK15常见多态性的影响，在未来开发针对TASK通道的药物时需要仔细考虑。我们的观察结果提供了在功能层面上研究 TASK-5 的途径，特别是在与 KCNK15 相关的恶性癌症中。© 2024。作者。

TASK-5 (KCNK15) belongs to the acid-sensitive subfamily of two-pore domain potassium (K2P) channels, which includes TASK-1 and TASK-3. TASK-5 stands out as K2P channel for which there is no functional data available, since it was reported in 2001 as non-functional and thus "silent". Here we show that TASK-5 channels are indeed non-functional as homodimers, but are involved in the formation of functional channel complexes with TASK-1 and TASK-3. TASK-5 negatively modulates the surface expression of TASK channels, while the heteromeric TASK-5-containing channel complexes located at the plasma membrane are characterized by changes in single-channel conductance, Gq-coupled receptor-mediated channel inhibition, and sensitivity to TASK modulators. The unique pharmacology of TASK-1/TASK-5 heterodimers, affected by a common polymorphism in KCNK15, needs to be carefully considered in the future development of drugs targeting TASK channels. Our observations provide an access to study TASK-5 at the functional level, particularly in malignant cancers associated with KCNK15.© 2024. The Author(s).