TASK‐2 channels contribute to pH sensitivity of retrotrapezoid nucleus chemoreceptor neurons (872.4)

Phox2b‐expressing neurons of the retrotrapezoid nucleus (RTN) function as central respiratory chemoreceptors; they are directly activated by CO 2 /H + , via an unidentified pH‐sensitive background K + channel, to drive breathing. Here, we test the effect of TASK2 (K2P5, an alkaline‐activated background K + channel) channel deletion on the pH sensitivity of RTN neurons and on CO 2 modulation of central respiratory output. For patch clamp recordings in brainstem slices, individual RTN neurons were identified by GFP expression (driven by the Phox2b promoter) or β‐galactosidase (from the gene trap used for TASK2 deletion). Whereas 95% of RTN cells from control mice were pH sensitive, only 56% from TASK2 ‐/‐ mice were classified as pH sensitive; the remaining cells were pH insensitive (44%). The alkaline‐activated background K + currents were reduced in amplitude in pH‐sensitive RTN neurons from TASK2 ‐/‐ mice but were absent from pH‐insensitive cells. TASK2 was strongly expressed in 63% of Phox2b‐expressing RTN neurons (by X‐gal staining), and in 85% (by a more sensitive scPCR approach). Using an in situ working heart‐brainstem preparation, we found diminished inhibition of phrenic burst amplitude by alkalization in TASK2 ‐/‐ mice, with apneic threshold shifted to higher pH levels. We conclude that TASK2 channels represent a molecular substrate for pH sensing in RTN respiratory chemoreceptor neurons. Grant Funding Source : Supported by: NIH HL074011 and NIH HL108609; and ANR‐RESPITASK and ANR‐11‐LABX‐0015‐01