TASK-2 channels contribute to pH sensitivity of retrotrapezoid nucleus chemoreceptor neurons

Sheng Wang, Najate Benamer, Sébastien Zanella, Natasha N. Kumar, Yingtang Shi, Michelle Bévengut, David Penton, Patrice G. Guyenet, Florian Lesage, Christian Gestreau*, Jacques Barhanin, Douglas A. Bayliss

*Corresponding author for this work

    Research output: Contribution to journalArticle

    64 Citations (Scopus)

    Abstract

    Phox2b-expressing glutamatergic neurons of the retrotrapezoid nucleus (RTN) display properties expected of central respiratory chemoreceptors; they are directly activated by CO2/H+ via an unidentified pH-sensitive background K+ channel and, in turn, facilitate brainstem networks that control breathing. Here, we used a knock-out mouse model to examine whether TASK-2 (K2P5), an alkaline-activated background K+ channel, contributes to RTN neuronal pH sensitivity. We made patch-clamp recordings in brainstem slices from RTN neurons that were identified by expression of GFP (directed by the Phox2b promoter) or β-galactosidase (from the gene trap used for TASK-2 knock-out). Whereas nearly all RTN cells from control mice were pH sensitive (95%, n=58 of 61), only 56% of GFP-expressing RTN neurons from TASK-2-/- mice (n-49 of 88) could be classified as pH sensitive (>30% reduction in firing rate from pH 7.0 to pH 7.8); the remaining cells were pH insensitive (44%). Moreover, none of the recorded RTN neurons from TASK-2-/- mice selected based on β-galactosidase activity (a subpopulation of GFP-expressing neurons) were pH sensitive. The alkaline-activated background K+ currents were reduced in amplitude in RTN neurons from TASK-2-/- mice that retained some pH sensitivity but were absent from pH-insensitive cells. Finally, using a working heart- brainstem preparation, we found diminished inhibition of phrenic burst amplitude by alkalization in TASK-2-/- mice, with apneic threshold shifted to higher pH levels. In conclusion, alkaline-activated TASK-2 channels contribute to pH sensitivity in RTN neurons, with effects on respiration in situ that are particularly prominent near apneic threshold.

    Original languageEnglish
    Pages (from-to)16033-16044
    Number of pages12
    JournalJournal of Neuroscience
    Volume33
    Issue number41
    DOIs
    Publication statusPublished - 2013

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    Wang, S., Benamer, N., Zanella, S., Kumar, N. N., Shi, Y., Bévengut, M., ... Bayliss, D. A. (2013). TASK-2 channels contribute to pH sensitivity of retrotrapezoid nucleus chemoreceptor neurons. Journal of Neuroscience, 33(41), 16033-16044. https://doi.org/10.1523/JNEUROSCI.2451-13.2013