TY - JOUR
T1 - TASK-2 channels contribute to pH sensitivity of retrotrapezoid nucleus chemoreceptor neurons
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.
PY - 2013
Y1 - 2013
N2 - 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.
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.
UR - http://www.scopus.com/inward/record.url?scp=84885104437&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.2451-13.2013
DO - 10.1523/JNEUROSCI.2451-13.2013
M3 - Article
C2 - 24107938
AN - SCOPUS:84885104437
SN - 0270-6474
VL - 33
SP - 16033
EP - 16044
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 41
ER -