PUBLICATION
Zebrafish and mouse TASK-2 K+ channels are inhibited by increased CO2 and intracellular acidification
- Authors
- Peña-Münzenmayer, G., Niemeyer, M.I., Sepúlveda, F.V., and Cid, L.P.
- ID
- ZDB-PUB-131105-3
- Date
- 2014
- Source
- Pflugers Archiv : European journal of physiology 466(7): 1317-27 (Journal)
- Registered Authors
- Keywords
- K2P K+ channels, Zebrafish TASK-2, Mouse TASK-2, CO2, Intracellular pH
- MeSH Terms
-
- Action Potentials
- Amino Acid Sequence
- Animals
- Carbon Dioxide/metabolism*
- Carbon Dioxide/pharmacology
- Carbonic Anhydrase Inhibitors/pharmacology
- Gills/cytology
- Gills/metabolism
- HEK293 Cells
- Humans
- Hydrogen-Ion Concentration
- Mice
- Molecular Sequence Data
- Mutation
- Neurons/drug effects
- Neurons/metabolism*
- Neurons/physiology
- Potassium Channels, Tandem Pore Domain/chemistry
- Potassium Channels, Tandem Pore Domain/genetics
- Potassium Channels, Tandem Pore Domain/metabolism*
- Protein Structure, Tertiary
- Zebrafish
- Zebrafish Proteins/chemistry
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 24081451 Full text @ Pflügers Archiv. / Eur. J. Physiol.
Citation
Peña-Münzenmayer, G., Niemeyer, M.I., Sepúlveda, F.V., and Cid, L.P. (2014) Zebrafish and mouse TASK-2 K+ channels are inhibited by increased CO2 and intracellular acidification. Pflugers Archiv : European journal of physiology. 466(7):1317-27.
Abstract
TASK-2 is a K2P K+ channel considered as a candidate to mediate CO2 sensing in central chemosensory neurons in mouse. Neuroepithelial cells in zebrafish gills sense CO2 levels through an unidentified K2P K+ channel. We have now obtained zfTASK-2 from zebrafish gill tissue that is 49 % identical to mTASK-2. Like its mouse equivalent, it is gated both by extra- and intracellular pH being activated by alkalinization and inhibited by acidification. The pHi dependence of zfTASK-2 is similar to that of mTASK-2, with pK
1/2 values of 7.9 and 8.0, respectively, but pHo dependence occurs with a pK
1/2 of 8.8 (8.0 for mTASK-2) in line with the relatively alkaline plasma pH found in fish. Increasing CO2 led to a rapid, concentration-dependent (IC50 ~1.5 % CO2) inhibition of mouse and zfTASK-2 that could be resolved into an inhibition by intracellular acidification and a CO2 effect independent of pHi change. Indeed a CO2 effect persisted despite using strongly buffered intracellular solutions abolishing any change in pHi, was present in TASK-2-K245A mutant insensitive to pHi, and also under carbonic anhydrase inhibition. The mechanism by which TASK-2 senses CO2 is unknown but requires the presence of the 245–273 stretch of amino acids in the C terminus that comprises numerous basic amino acids and is important in TASK-2 G protein subunit binding and regulation of the channel. The described CO2 effect might be of importance in the eventual roles played by TASK-2 in chemoreception in mouse and zebrafish.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping