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

Jungbauer, Stefan and Buehler, Philipp Karl and Neubauer, Jacqueline and Haas, Cordula and Heitzmann, Dirk and Tegtmeier, Ines and Sterner, Christina and Barhanin, Jacques and Georgieff, Michael and Warth, Richard and Thomas, Jorg (2017) Sex-dependent differences in the in vivo respiratory phenotype of the TASK-1 potassium channel knockout mouse. RESPIRATORY PHYSIOLOGY & NEUROBIOLOGY, 245. pp. 13-28. ISSN 1569-9048, 1878-1519

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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% O-2), hypoxia and hypercapnia was unaffected. Under acute hypoxia male TASK-1(-/-) mice exhibited a reduced increase of the respiratory frequency (f(R)) compared to wildtypes. However, the tidal volume (V-T) 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 f(R) under control condition (21% O-2). 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 (R-T), 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. (C) 2016 Elsevier B.V. All rights reserved.

Item Type: Article
Uncontrolled Keywords: INFANT-DEATH-SYNDROME; PULMONARY ARTERIAL-HYPERTENSION; DOMAIN K+ CHANNEL; CAROTID-BODY; VENTILATORY RESPONSES; BRAIN-STEM; INHALATION ANESTHETICS; CHEMORECEPTOR NEURONS; PH SENSITIVITY; GLOMUS CELLS; TASK-1 channel; Whole body plethysmograph; Sex-dependent; Chemoreception; Neonatal mice
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Biology, Preclinical Medicine > Institut für Physiologie
Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Richard Warth
Depositing User: Dr. Gernot Deinzer
Date Deposited: 14 Dec 2018 13:19
Last Modified: 18 Feb 2019 13:08
URI: https://pred.uni-regensburg.de/id/eprint/1933

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