Zebrafish and mouse task-2 k+ channels are inhibited by increased co2 and intracellular acidification
| Autor: | L. Pablo Cid, Francisco V. Sepúlveda, María Isabel Niemeyer, Gaspar Peña-Münzenmayer |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Gills
Physiology G protein Protein subunit Intracellular pH Molecular Sequence Data Clinical Biochemistry Mutant Action Potentials Mice Potassium Channels Tandem Pore Domain Physiology (medical) Carbonic anhydrase Animals Humans Amino Acid Sequence Carbonic Anhydrase Inhibitors Zebrafish Neurons chemistry.chemical_classification biology Carbon Dioxide Hydrogen-Ion Concentration Zebrafish Proteins biology.organism_classification Protein Structure Tertiary Cell biology Amino acid HEK293 Cells Biochemistry chemistry Mutation biology.protein Intracellular |
| Zdroj: | PFLUGERS ARCHIV Artículos CONICYT CONICYT Chile instacron:CONICYT |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|