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TASK-2 K2P K+ channel: thoughts about gating and its fitness to physiological function

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Abstract

TASK-2 (K2P5) was one of the earliest members of the K2P two-pore, four transmembrane domain K+ channels to be identified. TASK-2 gating is controlled by changes in both extra- and intracellular pH through separate sensors: arginine 224 and lysine 245, located at the extra- and intracellular ends of transmembrane domain 4. TASK-2 is inhibited by a direct effect of CO2 and is regulated by and interacts with G protein subunits. TASK-2 takes part in regulatory adjustments and is a mediator in the chemoreception process in neurons of the retrotrapezoid nucleus where its pHi sensitivity could be important in regulating excitability and therefore signalling of the O2/CO2 status. Extracellular pH increases brought about by HCO3 − efflux from proximal tubule epithelial cells have been proposed to couple to TASK-2 activation to maintain electrochemical gradients favourable to HCO3 − reabsorption. We demonstrate that, as suspected previously, TASK-2 is expressed at the basolateral membrane of the same proximal tubule cells that express apical membrane Na+-H+-exchanger NHE-3 and basolateral membrane Na+-HCO3 − cotransporter NBCe1-A, the main components of the HCO3 − transport machinery. We also discuss critically the mechanism by which TASK-2 is modulated and impacts the process of HCO3 − reclaim by the proximal tubule epithelium, concluding that more than a mere shift in extracellular pH is probably involved.

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Notes

  1. At pHo 7.4: [HCO3 −]i 24 mM, [HCO3 −]o 24 mM, [Na+]i 20 mM, [Na+]o 140 mM, Em −45 mV; ΔG for the outward movement of ions through the NBCe1-A for a stoichiometry of 1:3 is −3,669 J/mol. At pHo 8.0: [HCO3 −]i 24 mM, [HCO3 −]o 100 mM, [Na+]i 20 mM, [Na+]o 140 mM, Em −45 mV; ΔG =7,364 J/mol.

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Acknowledgments

The work in the authors’ laboratory is funded by FONDECYT grant 1110774. The Centro de Estudios Científicos (CECs) is funded by the Centres of Excellence Base Financing Programme of Conicyt. We are grateful to Drs. Masatake Araki and Kimi Araki from Kumamoto University, Japan for providing the TASK-2 KO mice, and to Dr. Ashley M. Toye from the University of Bristol, UK, for providing the NBCe1-A clone.

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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

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  1. Centro de Estudios Científicos (CECs), Avenida Arturo Prat 514, 5110466, Valdivia, Chile

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

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Correspondence to L. Pablo Cid.

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Karen I. López-Cayuqueo and Gaspar Peña-Münzenmayer contributed equally to this work.

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López-Cayuqueo, K.I., Peña-Münzenmayer, G., Niemeyer, M.I. et al. TASK-2 K2P K+ channel: thoughts about gating and its fitness to physiological function. Pflugers Arch - Eur J Physiol 467, 1043–1053 (2015). https://doi.org/10.1007/s00424-014-1627-7

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