Task2 potassium channels set central respiratory CO2 and O2 sensitivity.
Task2 K(+) channel expression in the central nervous system is surprisingly restricted to a few brainstem nuclei, including the retrotrapezoid (RTN) region. All Task2-positive RTN neurons were lost in mice bearing a Phox2b mutation that causes the human congenital central hypoventilation syndrome. In plethysmography, Task2(-/-) mice showed disturbed chemosensory function with hypersensitivity to low CO(2) concentrations, leading to hyperventilation. Task2 probably is needed to stabilize the membrane potential of chemoreceptive cells. In addition, Task2(-/-) mice lost the long-term hypoxia-induced respiratory decrease whereas the acute carotid-body-mediated increase was maintained. The lack of anoxia-induced respiratory depression in the isolated brainstem-spinal cord preparation suggested a central origin of the phenotype. Task2 activation by reactive oxygen species generated during hypoxia could silence RTN neurons, thus contributing to respiratory depression. These data identify Task2 as a determinant of central O(2) chemoreception and demonstrate that this phenomenon is due to the activity of a small number of neurons located at the ventral medullary surface.
Department of Neurovegetative Physiology, Centre National de la Recherche Scientifique, Université Paul Cézanne, 13397 Marseille, France.
Christian
C
Gestreau
Dirk
D
Heitzmann
Joerg
J
Thomas
Véronique
V
Dubreuil
Sascha
S
Bandulik
Markus
M
Reichold
Saïd
S
Bendahhou
Patricia
P
Pierson
Christina
C
Sterner
Julie
J
Peyronnet-Roux
Chérif
C
Benfriha
Ines
I
Tegtmeier
Hannah
H
Ehnes
Michael
M
Georgieff
Florian
F
Lesage
Jean-Francois
JF
Brunet
Christo
C
Goridis
Richard
R
Warth
Jacques
J
Barhanin
D000818:Animals; D000831:Animals, Newborn; D001933:Brain Stem / Q000473:pathology / Q000502:physiology / Q000503:physiopathology; D002245:Carbon Dioxide / Q000502:physiology*; D002628:Chemoreceptor Cells / Q000473:pathology / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology; D006801:Humans; D006935:Hypercapnia / Q000503:physiopathology; D000860:Hypoxia / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D010100:Oxygen / Q000502:physiology*; D010993:Plethysmography, Whole Body; D024683:Potassium Channels, Tandem Pore Domain / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011247:Pregnancy; D012125:Respiratory Center / Q000502:physiology*; D012143:Respiratory Physiological Phenomena; D020182:Sleep Apnea, Central / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology
D018398:Homeodomain Proteins; C498739:Kcnk5 protein, mouse; C109220:NBPhox protein; D024683:Potassium Channels, Tandem Pore Domain; D014157:Transcription Factors; D002245:Carbon Dioxide; D010100:Oxygen