Modulation of the Two-pore Domain Acid-sensitive K⁺ Channel TASK-2 (KCNK5) by Changes in Cell Volume

The molecular identity of K⁺ channels involved in Ehrlich cell volume regulation is unknown. A background K⁺ conductance is activated by cell swelling and is also modulated by extracellular pH. These characteristics are most similar to those of newly emerging TASK (TWIK-related acid-sensitive K⁺ channels)-type of two pore-domain K⁺ channels. mTASK-2, but not TASK-1 or -3, is present in Ehrlich cells and mouse kidney tissue from where the full coding sequences were obtained. Heterologous expression of mTASK-2 cDNA in HEK-293 cells generated K⁺ currents in the absence intracellular Ca²⁺. Exposure to hypotonicity enhanced mTASK-2 currents and osmotic cell shrinkage led to inhibition. This occurred without altering voltage dependence and with only slight decrease in pK _a in hypotonicity but no change in hypertonicity. Replacement with other cations yields a permselectivity sequence for mTASK-2 of K⁺ > Rb⁺ ≫ Cs⁺ > NH⁺ > Na⁺ ≒ Li⁺, similar to that for the native conductance (I_{K, vol}). Clofilium, a quaternary ammonium blocker of I_{K, vol}, blocked the mTASK-2-mediated K⁺ current with an IC₅₀ of 25 μM. The presence of mTASK-2 in Ehrlich cells, its functional similarities with I_{K, vol}, and its modulation by changes in cell volume suggest that this two-pore domain K⁺ channel participates in the regulatory volume decrease phenomenon.