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This Article Full Text Full Text (PDF) All Versions of this Article: 295/2/R649    most recent 00876.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Soliz, J. Articles by Gassmann, M. Search for Related Content PubMed PubMed Citation Articles by Soliz, J. Articles by Gassmann, M.

EXERCISE AND RESPIRATORY PHYSIOLOGY

Ventilatory responses to acute and chronic hypoxia are altered in female but not male Paskin-deficient mice

¹Institute of Veterinary Physiology, Vetsuisse Faculty, and Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland; ²Laboratoire de Physiologie Intégrative Cellulaire et Moléculaire, UMR Centre National de la Recherche Scientifique 5123 Villeurbanne, France; ³Institute of Physiology and ZIHP, University of Zürich, Zürich, Switzerland; and ⁴Department of Anesthesiology, University of Colorado Denver Health Sciences Center, Denver, Colorado

Submitted 9 December 2007 ; accepted in final form 21 May 2008

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.

ventilatory control; hypoxia; gender differences; oxygen sensing; carotid bodies