title: Perinatal hypoxia enhances cyclic adenosine monophosphate-mediated BKCa channel activation in adult murine pulmonary artery.
abstract: Exposure to perinatal hypoxia results in alteration of the adult pulmonary circulation, which is linked among others to alterations in K(+) channels in pulmonary artery (PA) smooth muscle cells. In particular, large conductance Ca(2+)-activated K(+) (BK(Ca)) channels protein expression and activity were increased in adult PA from mice born in hypoxia compared with controls. We evaluated long-term effects of perinatal hypoxia on the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) pathway-mediated activation of BK(Ca) channels, using isoproterenol, forskolin, and dibutyryl-cAMP. Whole-cell outward current was higher in pulmonary artery smooth muscle cells from mice born in hypoxia compared with controls. Spontaneous transient outward currents, representative of BK(Ca) activity, were present in a greater proportion in pulmonary artery smooth muscle cells of mice born in hypoxia than in controls. Agonists induced a greater relaxation in PA of mice born in hypoxia compared with controls, and BK(Ca) channels contributed more to the cAMP/PKA-mediated relaxation in case of perinatal hypoxia. In summary, perinatal hypoxia enhanced cAMP-mediated BK(Ca) channels activation in adult murine PA, suggesting that this pathway could be a potential target for modulating adult pulmonary vascular tone after perinatal hypoxia.
authors.affiliation: Laboratory of Vascular Cell Physiology, Department of Zoology and Animal Biology, University of Geneva, Geneva, Switzerland. mathieu.marino@unige.ch
authors.forename: Mathieu
authors.initials: M
authors.lastname: Marino
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Bény
authors.forename: Anne-Christine
authors.initials: AC
authors.lastname: Peyter
authors.forename: Giacomo
authors.initials: G
authors.lastname: Diaceri
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Tolsa
mesh_terms: D000367:Age Factors; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D005260:Female; D000860:Hypoxia / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism*; D011651:Pulmonary Artery / Q000187:drug effects / Q000378:metabolism*
chemical_list: C530995:BKCa protein, mouse; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D005576:Colforsin; D000242:Cyclic AMP; D007545:Isoproterenol