期刊
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
卷 293, 期 5, 页码 L1171-L1182出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajplung.00126.2007
关键词
mouse; potassium ion channel activity; potassium ion channel blockers; nitric oxide donors
Adverse events during the perinatal period, like hypoxia, have been associated with adult diseases. In pulmonary vessels, K+ channels play an important role in the regulation of vascular tone. In the fetus, Ca2+-activated K+ channels (K-Ca) are predominant, whereas from birth voltage-gated K+ channels (K-V) prevail in the adult. We postulated that perinatal hypoxia could alter this maturational shift and influence regulation of pulmonary vascular tone in relation to K+ channels in adulthood. We evaluated the effects of perinatal hypoxia on KV and KCa channels in the adult main pulmonary artery (PA) using a murine model. Electrophysiological measurements showed a greater outward current in PA smooth muscle cells of mice born in hypoxia than in controls. In controls, only KV channels contributed to this current, whereas in mice born in hypoxia both KV and KCa channels were implicated. KV channel activity was even higher in mice born in hypoxia than in controls. Therefore, perinatal hypoxia results in increased KCa and KV channel activity in adult PA. Moreover, PA of adults born in hypoxia displayed higher large-conductance K-Ca alpha-subunit and K(V)1.5 alpha-subunit protein expression than controls. Interestingly, relaxation induced by nitric oxide (NO) donors [S-nitroso-N-acetyl-D,L-penicillamine, 2-(N,N-diethylamino)-diazenolate-2-oxide] in isolated PA of control mice was not mediated by KCa channels and only slightly by KV channels, whereas following perinatal hypoxia both KCa and KV channels contributed to this relaxation. Thus perinatal hypoxia results in altered expression and activity of different K+ channels in the adult main PA, which could contribute to modifications of pulmonary vasoreactivity.
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