| First Author | Buehler PK | Year | 2017 |
| Journal | Respir Physiol Neurobiol | Volume | 244 |
| Pages | 17-25 | PubMed ID | 28673876 |
| Mgi Jnum | J:271837 | Mgi Id | MGI:6282212 |
| Doi | 10.1016/j.resp.2017.06.009 | Citation | Buehler PK, et al. (2017) Abnormal respiration under hyperoxia in TASK-1/3 potassium channel double knockout mice. Respir Physiol Neurobiol 244:17-25 |
| abstractText | Despite intensive research, the exact function of TASK potassium channels in central and peripheral chemoreception is still under debate. In this study, we investigated the respiration of unrestrained TASK-3 (TASK-3(-/-)) and TASK-1/TASK-3 double knockout (TASK-1/3(-/-)) adult male mice in vivo using a plethysmographic device. Ventilation parameters of TASK-3(-/-) mice were normal under control condition (21% O2) and upon hypoxia and hypercapnia they displayed the physiological increase of ventilation. TASK-1/3(-/-) mice showed increased ventilation under control conditions. This increase of ventilation was caused by increased tidal volumes (VT), a phenomenon similarly observed in TASK-1(-/-) mice. Under acute hypoxia, TASK-1/3(-/-) mice displayed the physiological increase of the minute volume. Interestingly, this increase was not related to an increase of the respiratory frequency (fR), as observed in wild-type mice, but was caused by a strong increase of VT. This particular respiratory phenotype is reminiscent of the respiratory phenotype of carotid body-denervated rodents in the compensated state. Acute hypercapnia (5% CO2) stimulated ventilation in TASK-1/3(-/-) and wild-type mice to a similar extent; however, at higher CO2 concentrations (>5% CO2) the stimulation of ventilation was more pronounced in TASK-1/3(-/-) mice. At hyperoxia (100% O2), TASK-1(-/-), TASK-3(-/-) and wild-type mice showed the physiological small decrease of ventilation. In sharp contrast, TASK-1/3(-/-) mice exhibited an abnormal increase of ventilation under hyperoxia. In summary, these measurements showed a grossly normal respiration of TASK-3(-/-) mice and a respiratory phenotype of TASK-1/3(-/-) mice that was characterized by a markedly enhanced tidal volume, similar to the one observed in TASK-1(-/-) mice. The abnormal hyperoxia response, exclusively found in TASK-1/3(-/-) double mutant mice, indicates that both TASK-1 and TASK-3 are essential for the hyperoxia-induced hypoventilation. The peculiar respiratory phenotype of TASK-1/3 knockout mice is reminiscent of the respiration of animals with long-term carotid body dysfunction. Taken together, TASK-1 and TASK-3 appear to serve specific and distinct roles in the complex processes underlying chemoreception and respiratory control. |
