Zebrafish and mouse TASK-2 K+ channels are inhibited by increased CO2 and intracellular acidification

TASK-2 is a K 2P K + channel considered as a candidate to mediate CO 2 sensing in central chemosensory neurons in mouse. Neuroepithelial cells in zebrafish gills sense CO 2 levels through an unidentified K 2P 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 pH i dependence of zfTASK-2 is similar to that of mTASK-2, with p K 1/2 values of 7.9 and 8.0, respectively, but pH o dependence occurs with a p K 1/2 of 8.8 (8.0 for mTASK-2) in line with the relatively alkaline plasma pH found in fish. Increasing CO 2 led to a rapid, concentration-dependent (IC 50 ~1.5 % CO 2 ) inhibition of mouse and zfTASK-2 that could be resolved into an inhibition by intracellular acidification and a CO 2 effect independent of pH i change. Indeed a CO 2 effect persisted despite using strongly buffered intracellular solutions abolishing any change in pH i , was present in TASK-2-K245A mutant insensitive to pH i , and also under carbonic anhydrase inhibition. The mechanism by which TASK-2 senses CO 2 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 CO 2 effect might be of importance in the eventual roles played by TASK-2 in chemoreception in mouse and zebrafish.