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

• Published in: The Journal of biological chemistry 2001-11, Vol.276 (46), p.43166-43174
• Main Authors: Niemeyer, M I, Cid, L P, Barros, L F, Sepúlveda, F V
• Format: Article
• Language: English
• Subjects: Animals; Blotting, Northern; Carcinoma, Ehrlich Tumor; Cations; Cell Line; DNA, Complementary - metabolism; Dose-Response Relationship, Drug; Electrophysiology; Humans; Hydrogen-Ion Concentration; Immunoblotting; Kidney - metabolism; Mice; Polymerase Chain Reaction; Potassium - metabolism; Potassium Channels - chemistry; Potassium Channels - metabolism; Potassium Channels, Tandem Pore Domain; Protein Binding; Protein Structure, Tertiary; Quaternary Ammonium Compounds - pharmacology; RNA - metabolism; RNA, Messenger - metabolism; Time Factors; Transfection
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M107192200

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 Ca 2+ . 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 p K 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 IC 50 of 25 μ m . 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.