Ventilatory responses to acute and chronic hypoxia are altered in female but not male Paskin-deficient mice.
Proteins harboring a Per-Arnt-Sim (PAS) domain are versatile and allow archaea, bacteria, and plants to sense oxygen partial pressure, as well as light intensity and redox potential. A PAS domain associated with a histidine kinase domain is found in FixL, the oxygen sensor molecule of Rhizobium species. PASKIN is the mammalian homolog of FixL, but its function is far from being understood. Using whole body plethysmography, we evaluated the ventilatory response to acute and chronic hypoxia of homozygous deficient male and female PASKIN mice (Paskin-/-). Although only slight ventilatory differences were found in males, female Paskin-/- mice increased ventilatory response to acute hypoxia. Unexpectedly, females had an impaired ability to reach ventilatory acclimatization in response to chronic hypoxia. Central control of ventilation occurs in the brain stem respiratory centers and is modulated by catecholamines via tyrosine hydroxylase (TH) activity. We observed that TH activity was altered in male and female Paskin-/- mice. Peripheral chemoreceptor effects on ventilation were evaluated by exposing animals to hyperoxia (Dejours test) and domperidone, a peripheral ventilatory stimulant drug directly affecting the carotid sinus nerve discharge. Male and female Paskin-/- had normal peripheral chemosensory (carotid bodies) responses. In summary, our observations suggest that PASKIN is involved in the central control of hypoxic ventilation, modulating ventilation in a gender-dependent manner.
Institute of Veterinary Physiology, Vetsuisse Faculty and Zurich Center for Integrative Human Physiology, ZIHP Winterthurerstrasse 260, CH-8057 Zurich, Switzerland. jsoliz@access.uzh.ch
Jorge
J
Soliz
Christophe
C
Soulage
Emanuela
E
Borter
Martha Tissot
MT
van Patot
Max
M
Gassmann
D000064:Acclimatization; D000208:Acute Disease; D000818:Animals; D001831:Body Temperature; D002344:Carotid Body / Q000378:metabolism / Q000503:physiopathology; D002908:Chronic Disease; D004195:Disease Models, Animal; D004294:Domperidone / Q000494:pharmacology; D005260:Female; D018496:Hyperoxia / Q000378:metabolism / Q000503:physiopathology; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption; D010993:Plethysmography, Whole Body; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D012123:Pulmonary Ventilation / Q000187:drug effects; D012125:Respiratory Center / Q000201:enzymology; D015656:Respiratory Mechanics; D012737:Sex Factors; D013990:Tidal Volume; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D004294:Domperidone; D014446:Tyrosine 3-Monooxygenase; C116037:PAS domain kinases; D017346:Protein Serine-Threonine Kinases; D010100:Oxygen