Hydrogen peroxide selectively increases TREK-2 currents via myosin light chain kinases.
Two-pore domain K+ (K2P) channels play a critical role in cellular responses to various stimuli, such as stretch or changes in pH and are considered to be important in pathological responses such as apoptosis and tumorigenesis. We investigated effects of H2O2 on various K2P channels expressed in CHO cells. Application of H2O2 did not affect TASK-1, TASK-3, TRAAK currents, but specifically increased TREK-2 currents recorded using a nystatin perforated whole cell technique. The H2O2-induced activation of TREK-2 currents was also observed at single channel levels in cell-attached patches, and the effect was reversed by the reducing agent, dithiothreitol. In contrast, TREK-2 currents recorded using ruptured whole cell technique or single channel recording in inside-out patches were not affected by H2O2. Furthermore, direct application of 5,5'-dithiobis-(2-nitrobenzoic acid) inhibited TREK-2, suggesting that the H2O2-induced activation does not result from direct oxidation of TREK-2 proteins. Among the cell signaling agents, myosin light chain kinase (MLCK) inhibitors significantly inhibited the H2O2-induced activation of TREK-2 currents. These results suggest that TREK-2 channels have a potential to play a specific role in cellular responses to reactive oxygen species and that MLCK activation is involved in this process.
Kim
Yangmi
Y
Department of Physiology, College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju, 361-763, Korea.
Lee
Suk-Ho
SH
Ho
Won-Kyung
WK
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004553:Electric Conductivity; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D009219:Myosin-Light-Chain Kinase / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018408:Patch-Clamp Techniques; D024683:Potassium Channels, Tandem Pore Domain / Q000378:metabolism*; D015398:Signal Transduction
D009419:Nerve Tissue Proteins; D024683:Potassium Channels, Tandem Pore Domain; C420132:potassium channel subfamily K member 3; D006861:Hydrogen Peroxide; D009219:Myosin-Light-Chain Kinase