Header

UZH-Logo

Maintenance Infos

Sex-dependent differences in the in vivo respiratory phenotype of the TASK-1 potassium channel knockout mouse


Jungbauer, Stefan; Buehler, Philipp Karl; Neubauer, Jacqueline; Haas, Cordula; Heitzmann, Dirk; Tegtmeier, Ines; Sterner, Christina; Barhanin, Jacques; Georgieff, Michael; Warth, Richard; Thomas, Jörg (2016). Sex-dependent differences in the in vivo respiratory phenotype of the TASK-1 potassium channel knockout mouse. Respiratory Physiology & Neurobiology:Epub ahead of print.

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 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.

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 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.

Statistics

Citations

Altmetrics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Legal Medicine
04 Faculty of Medicine > University Children's Hospital Zurich > Clinic for Surgery
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2016
Deposited On:13 Dec 2016 12:45
Last Modified:29 Dec 2016 13:51
Publisher:Elsevier
ISSN:1569-9048
Publisher DOI:https://doi.org/10.1016/j.resp.2016.11.005
PubMed ID:27838333

Download

Full text not available from this repository.
View at publisher

Article Networks

TrendTerms

TrendTerms displays relevant terms of the abstract of this publication and related documents on a map. The terms and their relations were extracted from ZORA using word statistics. Their timelines are taken from ZORA as well. The bubble size of a term is proportional to the number of documents where the term occurs. Red, orange, yellow and green colors are used for terms that occur in the current document; red indicates high interlinkedness of a term with other terms, orange, yellow and green decreasing interlinkedness. Blue is used for terms that have a relation with the terms in this document, but occur in other documents.
You can navigate and zoom the map. Mouse-hovering a term displays its timeline, clicking it yields the associated documents.

Author Collaborations