PT  - JOURNAL ARTICLE
AU  - Wang, Sheng
AU  - Benamer, Najate
AU  - Zanella, Sébastien
AU  - Kumar, Natasha N.
AU  - Shi, Yingtang
AU  - Bévengut, Michelle
AU  - Penton, David
AU  - Guyenet, Patrice G.
AU  - Lesage, Florian
AU  - Gestreau, Christian
AU  - Barhanin, Jacques
AU  - Bayliss, Douglas A.
TI  - TASK-2 Channels Contribute to pH Sensitivity of Retrotrapezoid Nucleus Chemoreceptor Neurons
AID  - 10.1523/JNEUROSCI.2451-13.2013
DP  - 2013 Oct 09
TA  - The Journal of Neuroscience
PG  - 16033--16044
VI  - 33
IP  - 41
4099  - http://www.jneurosci.org/content/33/41/16033.short
4100  - http://www.jneurosci.org/content/33/41/16033.full
SO  - J. Neurosci.2013 Oct 09; 33
AB  - 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.