TASK channels determine pH sensitivity in select respiratory neurons but do not contribute to central respiratory chemosensitivity.
Central respiratory chemoreception is the mechanism by which the CNS maintains physiologically appropriate pH and PCO2 via control of breathing. A prominent hypothesis holds that neural substrates for this process are distributed widely in the respiratory network, especially because many neurons that make up this network are chemosensitive in vitro. We and others have proposed that TASK channels (TASK-1, K(2P)3.1 and/or TASK-3, K(2P)9.1) may serve as molecular sensors for central chemoreception because they are highly expressed in multiple neuronal populations in the respiratory pathway and contribute to their pH sensitivity in vitro. To test this hypothesis, we examined the chemosensitivity of two prime candidate chemoreceptor neurons in vitro and tested ventilatory responses to CO2 using TASK channel knock-out mice. The pH sensitivity of serotonergic raphe neurons was abolished in TASK channel knock-outs. In contrast, pH sensitivity of neurons in the mouse retrotrapezoid nucleus (RTN) was fully maintained in a TASK null background, and pharmacological evidence indicated that a K+ channel with properties distinct from TASK channels contributes to the pH sensitivity of rat RTN neurons. Furthermore, the ventilatory response to CO2 was completely retained in single or double TASK knock-out mice. These data rule out a strict requirement for TASK channels or raphe neurons in central respiratory chemosensation. Furthermore, they indicate that a non-TASK K+ current contributes to chemosensitivity of RTN neurons, which are profoundly pH-sensitive and capable of driving respiratory output in response to local pH changes in vivo.
Mulkey
Daniel K
DK
Department of Pharmacology, University of Virginia, Charlottesville, Virginia 22908, USA.
Talley
Edmund M
EM
Stornetta
Ruth L
RL
Siegel
Audra R
AR
West
Gavin H
GH
Chen
Xiangdong
X
Sen
Neil
N
Mistry
Akshitkumar M
AM
Guyenet
Patrice G
PG
Bayliss
Douglas A
DA
D000818:Animals; D002478:Cells, Cultured; D002628:Chemoreceptor Cells / Q000502:physiology*; D006863:Hydrogen-Ion Concentration; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D009924:Organ Culture Techniques; D015221:Potassium Channels / Q000502:physiology*; D024683:Potassium Channels, Tandem Pore Domain / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011903:Raphe Nuclei / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012125:Respiratory Center / Q000166:cytology / Q000378:metabolism / Q000502:physiology*
D009419:Nerve Tissue Proteins; D015221:Potassium Channels; D024683:Potassium Channels, Tandem Pore Domain; C511784:TASK3 protein, mouse; C420132:potassium channel subfamily K member 3