OXYGEN-INDUCED CONSTRICTION OF RABBIT DUCTUS-ARTERIOSUS OCCURS VIA INHIBITION OF A 4-AMINOPYRIDINE-SENSITIVE, VOLTAGE-SENSITIVE POTASSIUM CHANNEL

The ductus arteriosus is a vital fetal structure allowing blood ejecte d from the right ventricle to bypass the pulmonary circulation in uter o. Closure of the ductus arteriosus at birth, essential for postnatal adaptation, is initiated by an increase in oxygen (O-2) tension, We re cently demonstrated the presence of O-2-sensitive potassium channels i n the fetal and adult pulmonary circulation which regulate vascular to ne in response to changes in O-2 tension, In this study, we assessed t he cellular mechanisms underlying O-2-induced constriction of the duct us arteriosus in late-gestation fetal rabbits. We report that O-2 reve rsibly inhibits a 58-pS voltage- and 4-aminopyridine-sensitive potassi um channel, causing membrane depolarization, an increase in intracellu lar calcium through L-type voltage-gated calcium channels, and constri ction of the ductus arteriosus. We conclude that the effector mechanis m for O-2 sensing in the ductus arteriosus involves the coordinated ac tion of delayed rectifier potassium channels and voltage-gated calcium channels.