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 regul ation 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+ cha nnels)-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 cod ing sequences were obtained. Heterologous expression of mTASK-2 cDNA in HEK -293 cells generated K+ currents in the absence intracellular Ca2+. Exposur e to hypotonicity enhanced mTASK-2 currents and osmotic cell shrinkage led to inhibition. This occurred without altering voltage dependence and with o nly slight decrease in pK(a) in hypotonicity but no change in hypertonicity . Replacement with other cations yields a permselectivity sequence for mTAS K-2 of K+ > Rb+ >> Cs+ > NH4+ > Na+ congruent to Li+, similar to that for t he native conductance (I-K,I- vol). Clofflium, a quaternary ammonium blocke r of I-K, (vol), blocked the mTASK-2-mediated K+ current with an IC50 of 25 mum. 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 decr ease phenomenon.