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

  • Ion channels, receptors and transporters
  • Published:
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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.

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Notes

  1. Notice that there are dissenting views on the validity of the metabolon concept [2, 5].

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Acknowledgments

This work was supported by FONDECYT grant 1110774. The Centro de Estudios Científicos (CECs) is funded by Centers of Excellence Base Financing Program of Conicyt. We are grateful to Dr. Wendy González (Talca) for her help with molecular modeling work and to Carlos Bórquez for his assistance.

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  1. Gaspar Peña-Münzenmayer

    Present address: National Institute of Dental and Craniofacial Research, National Institutes of Health, 10 Center Drive, Bethesda, MD, 20892, USA

Authors and Affiliations

  1. Centro de Estudios Científicos (CECs), Avenida Arturo Prat 514, Valdivia, Chile

    Gaspar Peña-Münzenmayer, María Isabel Niemeyer, Francisco V. Sepúlveda & L. Pablo Cid

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  1. Gaspar Peña-Münzenmayer
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  2. María Isabel Niemeyer
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Correspondence to L. Pablo Cid.

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Peña-Münzenmayer, G., Niemeyer, M.I., Sepúlveda, F.V. et al. Zebrafish and mouse TASK-2 K+ channels are inhibited by increased CO2 and intracellular acidification. Pflugers Arch - Eur J Physiol 466, 1317–1327 (2014). https://doi.org/10.1007/s00424-013-1365-2

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