Sex-dependent differences in the in vivo respiratory phenotype of the TASK-1 potassium channel knockout mouse
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...
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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
2017
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| In: |
Respiratory physiology & neurobiology
Year: 2016, Volume: 245, Pages: 13-28 |
| ISSN: | 1878-1519 |
| DOI: | 10.1016/j.resp.2016.11.005 |
| Online Access: | Verlag, Volltext: http://dx.doi.org/10.1016/j.resp.2016.11.005 Verlag, Volltext: http://www.sciencedirect.com/science/article/pii/S1569904816302671 
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| Author Notes: | Stefan Jungbauer, Philipp Karl Buehler, Jacqueline Neubauer, Cordula Haas, Dirk Heitzmann, Ines Tegtmeier, Christina Sterner, Jacques Barhanin, Michael Georgieff, Richard Warth, Jörg Thomas |
| Summary: | 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 fR under 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. |
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| Item Description: | Gesehen am 21.06.2018 Available online 10 November 2016 |
| Physical Description: | Online Resource |
| ISSN: | 1878-1519 |
| DOI: | 10.1016/j.resp.2016.11.005 |