title: Acid-sensitive TWIK and TASK two-pore domain potassium channels change ion selectivity and become permeable to sodium in extracellular acidification.
abstract: Two-pore domain K(+) channels (K2P) mediate background K(+) conductance and play a key role in a variety of cellular functions. Among the 15 mammalian K2P isoforms, TWIK-1, TASK-1, and TASK-3 K(+) channels are sensitive to extracellular acidification. Lowered or acidic extracellular pH (pH(o)) strongly inhibits outward currents through these K2P channels. However, the mechanism of how low pH(o) affects these acid-sensitive K2P channels is not well understood. Here we show that in Na(+)-based bath solutions with physiological K(+) gradients, lowered pH(o) largely shifts the reversal potential of TWIK-1, TASK-1, and TASK-3 K(+) channels, which are heterologously expressed in Chinese hamster ovary cells, into the depolarizing direction and significantly increases their Na(+) to K(+) relative permeability. Low pH(o)-induced inhibitions in these acid-sensitive K2P channels are more profound in Na(+)-based bath solutions than in channel-impermeable N-methyl-D-glucamine-based bath solutions, consistent with increases in the Na(+) to K(+) relative permeability and decreases in electrochemical driving forces of outward K(+) currents of the channels. These findings indicate that TWIK-1, TASK-1, and TASK-3 K(+) channels change ion selectivity in response to lowered pH(o), provide insights on the understanding of how extracellular acidification modulates acid-sensitive K2P channels, and imply that these acid-sensitive K2P channels may regulate cellular function with dynamic changes in their ion selectivity.
authors.affiliation: Department of Biological Sciences and the Center for Neuroscience Research, University at Albany, State University of New York, Albany, New York 12222, USA.
authors.forename: Liqun
authors.initials: L
authors.lastname: Ma
authors.forename: Xuexin
authors.initials: X
authors.lastname: Zhang
authors.forename: Min
authors.initials: M
authors.lastname: Zhou
authors.forename: Haijun
authors.initials: H
authors.lastname: Chen
mesh_terms: D020816:Amino Acid Motifs; D019943:Amino Acid Substitution; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D045604:Extracellular Fluid / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008564:Membrane Potentials; D051379:Mice; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010539:Permeability; D015221:Potassium Channels / Q000378:metabolism; D024683:Potassium Channels, Tandem Pore Domain / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D051381:Rats; D012964:Sodium / Q000378:metabolism*
chemical_list: D009419:Nerve Tissue Proteins; D015221:Potassium Channels; D024683:Potassium Channels, Tandem Pore Domain; D012964:Sodium; C498655:KCNK9 protein, human; C487530:Kcnk1 protein, rat; C103742:potassium channel protein TREK-1; C420132:potassium channel subfamily K member 3; C486498:Kcnk18 protein, mouse