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), ...
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.
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