TASK-1, TWIK-related acid-sensitive potassium channel 1, is a member of the two-pore- domain potassium channel family. It is constitutively active at resting potentials and strongly expressed in the heart. However, little is known about the role of TASK-1 channels in hypoxia. A cellular model of hypoxia and reoxygenation from rat heart-derived H9c2 cells or TASK-1 deficient HEK293T cells was employed to explore the role of TASK-1 channels in cytoprotection against hypoxia. The cell viability assay revealed that TASK-1 expression increased the number of viable cells subjected to 2 h of hypoxia followed by 2 h of reoxygenation (H/R). To dissect the protective role of TASK-1 on mitochondrial function, mitochondrial membrane potential (MMP) was assessed by tetramethylrhodamine fluorescence. It was demonstrated that MMP was significantly decreased by H/R, but it was maintained by TASK-1 expression or pretreatment with cyclosporin A, an inhibitor of mitochondrial permeability transition pore (mPTP). The effect of cyclosporin A on MMP was not further altered by TASK-1 expression. Moreover, TASK-1 expression significantly blocked cytochrome c release induced by H/R. While a small fraction of endogenous TASK-1 was found to colocalize with the mitochondrial marker MitoTracker in H9c2 cells, H/R did not alter the extent of colocalization of TASK-1 with MitoTracker. The total TASK-1 protein level was not significantly affected by H/R. In summary, we provided the evidence that TASK-1 channels confer cytoprotection against hypoxia-reoxygenation injury, possibly by their capacity of maintaining the mitochondrial membrane potential via inhibiting MPTP opening.

TASK-1，TWIK 相关酸敏感钾通道 1，是双孔结构域钾通道家族的成员。它在静息电位上具有组成性活性，并在心脏中强烈表达。然而，关于 TASK-1 通道在缺氧中的作用知之甚少。采用来自大鼠心脏来源的 H9c2 细胞或 TASK-1 缺陷型 HEK293T 细胞的缺氧和复氧细胞模型来探索 TASK-1 通道在细胞抗缺氧保护中的作用。细胞活力测定显示，TASK-1 表达增加了经受 2 小时缺氧和 2 小时复氧 (H/R) 的活细胞数量。为了剖析 TASK-1 对线粒体功能的保护作用，通过四甲基罗丹明荧光评估线粒体膜电位 (MMP)。结果表明，H/R 显着降低了 MMP，但通过 TASK-1 表达或用线粒体通透性转换孔 (mPTP) 抑制剂环孢菌素 A 预处理来维持 MMP。TASK-1 表达没有进一步改变环孢菌素 A 对 MMP 的影响。此外，TASK-1 表达显着阻断细胞色素c由 H/R 诱导的释放。虽然发现一小部分内源性 TASK-1 与 H9c2 细胞中的线粒体标记 MitoTracker 共定位，但 H/R 并未改变 TASK-1 与 MitoTracker 的共定位程度。总 TASK-1 蛋白水平不受 H/R 显着影响。总之，我们提供的证据表明，TASK-1 通道对缺氧-复氧损伤具有细胞保护作用，可能是通过它们通过抑制 MPTP 开放来维持线粒体膜电位的能力。