title: Sex-dependent differences in the in vivo respiratory phenotype of the TASK-1 potassium channel knockout mouse.
abstract: TASK-1 potassium channels have been implicated in central and peripheral chemoreception; however, the precise contribution of TASK-1 for the control of respiration is still under debate. Here, we investigated the respiration of unrestrained adult and neonatal TASK-1 knockout mice (TASK-1-/-) using a plethysmographic device. Respiration in adult female TASK-1-/-mice under control (21% O2), hypoxia and hypercapnia was unaffected. Under acute hypoxia male TASK-1-/-mice exhibited a reduced increase of the respiratory frequency (fR) compared to wildtypes. However, the tidal volume (VT) of male TASK-1-/-mice was strongly enhanced. The volatile anesthetic isoflurane induced in male TASK-1-/-and male wild type mice (TASK-1+/+) a similar respiratory depression. Neonatal TASK-1-/-mice demonstrated a 30-40% decrease of the minute volume, caused by a reduction of the fRunder control condition (21% O2). Under hypoxia, neonatal TASK-1-/-mice more frequently stopped breathing (apnea>3s) suggesting an increased hypoxia-sensitivity. As reported before, this increased hypoxia sensitivity had no influence on the survival rate of neonatal TASK-1-/-mice. In adult and neonatal mice, TASK-1 gene deletion induced a significant prolongation of the relaxation time (RT), which is a parameter for expiration kinetics. Additionally, screening for mutations in the human TASK-1 gene in 155 cases of sudden infant death syndrome (SIDS) was inconclusive. In conclusion, these data are suggestive for an increased hypoxia-sensitivity of neonatal TASK-1-/-mice, however, without causing an increase in neonatal lethality. In adult female TASK-1-/-mice respiration was unaffected, whereas adult male TASK-1-/-mice showed a modified breathing pattern. These results are suggestive for sex-specific mechanisms for compensating the inactivation of TASK-1 in mice.
authors.affiliation: Institute of Physiology, University of Regensburg, D-93053, Regensburg, Germany; University Hospital of Erlangen, Department of Internal Medicine 1, Ulmenweg 18, D-91054 Erlangen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Jungbauer
authors.affiliation: University Children's Hospital, Steinwiesstr. 75, CH-8032 Zürich, Switzerland.
authors.forename: Philipp Karl
authors.initials: PK
authors.lastname: Buehler
authors.affiliation: Institute of Forensic Medicine, University of Zurich, Switzerland.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Neubauer
authors.affiliation: Institute of Forensic Medicine, University of Zurich, Switzerland.
authors.forename: Cordula
authors.initials: C
authors.lastname: Haas
authors.affiliation: University Hospital of Mannheim, Department of Internal Medicine V, Theodor-Kutzer-Ufer 1-3,D-68167 Mannheim, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Heitzmann
authors.affiliation: Institute of Physiology, University of Regensburg, D-93053, Regensburg, Germany.
authors.forename: Ines
authors.initials: I
authors.lastname: Tegtmeier
authors.affiliation: Institute of Physiology, University of Regensburg, D-93053, Regensburg, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Sterner
authors.affiliation: Laboratories of Excellence, Ion channel Science and Therapeutics, Nice, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Barhanin
authors.affiliation: Institute of Anesthesiology, University of Ulm, D-89081 Ulm, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Georgieff
authors.affiliation: Institute of Physiology, University of Regensburg, D-93053, Regensburg, Germany.
authors.forename: Richard
authors.initials: R
authors.lastname: Warth
authors.affiliation: University Children's Hospital, Steinwiesstr. 75, CH-8032 Zürich, Switzerland. Electronic address: joergthomas@email.de.
authors.forename: Jörg
authors.initials: J
authors.lastname: Thomas
mesh_terms: D000375:Aging / Q000378:metabolism; D018685:Anesthetics, Inhalation / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D015331:Cohort Studies; D005260:Female; D006801:Humans; D006935:Hypercapnia / Q000503:physiopathology; D007223:Infant; D007530:Isoflurane / Q000494:pharmacology; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000172:deficiency* / Q000235:genetics; D010993:Plethysmography, Whole Body; D024683:Potassium Channels, Tandem Pore Domain / Q000172:deficiency* / Q000235:genetics; D012119:Respiration / Q000187:drug effects; D012727:Sex Characteristics; D013398:Sudden Infant Death / Q000235:genetics; D013990:Tidal Volume / Q000502:physiology
chemical_list: D018685:Anesthetics, Inhalation; D009419:Nerve Tissue Proteins; D024683:Potassium Channels, Tandem Pore Domain; C420132:potassium channel subfamily K member 3; D007530:Isoflurane
keywords: Chemoreception; Neonatal mice; Sex-dependent; TASK-1 channel; Whole body plethysmograph