Oxygen-induced constriction of rabbit ductus arteriosus occurs via inhibition of a 4-aminopyridine-, voltage-sensitive potassium channel.
The ductus arteriosus is a vital fetal structure allowing blood ejected from the right ventricle to bypass the pulmonary circulation in utero. Closure of the ductus arteriosus at birth, essential for postnatal adaptation, is initiated by an increase in oxygen (O2) tension. We recently demonstrated the presence of O2-sensitive potassium channels in the fetal and adult pulmonary circulation which regulate vascular tone in response to changes in O2 tension. In this study, we assessed the cellular mechanisms underlying O2-induced constriction of the ductus arteriosus in late-gestation fetal rabbits. We report that O2 reversibly inhibits a 58-pS voltage- and 4-aminopyridine-sensitive potassium channel, causing membrane depolarization, an increase in intracellular calcium through L-type voltage-gated calcium channels, and constriction of the ductus arteriosus. We conclude that the effector mechanism for O2 sensing in the ductus arteriosus involves the coordinated action of delayed rectifier potassium channels and voltage-gated calcium channels.
Department of Pediatrics, University of Minnesota, Minneapolis 55455, USA.
M
M
Tristani-Firouzi
H L
HL
Reeve
S
S
Tolarova
E K
EK
Weir
S L
SL
Archer
D015761:4-Aminopyridine / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000502:physiology; D046508:Culture Techniques; D004373:Ductus Arteriosus / Q000502:physiology*; D006321:Heart / Q000196:embryology*; D015640:Ion Channel Gating / Q000187:drug effects; D008564:Membrane Potentials; D010100:Oxygen / Q000502:physiology*; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology*; D011817:Rabbits
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D015761:4-Aminopyridine; D010100:Oxygen; D002118:Calcium