Publication
TASK-2 Channels Contribute to pH Sensitivity of Retrotrapezoid Nucleus Chemoreceptor Neurons
Publisher:
Society for Neuroscience
Date:
09-10-2013
DOI:
10.1523/JNEUROSCI.2451-13.2013
Abstract: Phox2b-expressing glutamatergic neurons of the retrotrapezoid nucleus (RTN) display properties expected of central respiratory chemoreceptors they are directly activated by CO 2 /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-cl 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 ( % 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 litude 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 litude 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.