TASK-1 regulates mitochondrial function under hypoxia

Abstract

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.