Oxygen-induced constriction of rabbit ductus arteriosus occurs via inhibition of a 4-aminopyridine-, voltage-sensitive potassium channel

Martin Tristani-Firouzi, Helen L. Reeve, Simona Tolarova, Edward K Weir, Stephen L. Archer

Research output: Contribution to journalArticlepeer-review

100 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1959-1965
Number of pages7
JournalJournal of Clinical Investigation
Volume98
Issue number9
DOIs
StatePublished - Nov 1 1996

Keywords

  • calcium
  • fetal physiology
  • ion channels
  • oxygen-sensing
  • vascular tone

Fingerprint Dive into the research topics of 'Oxygen-induced constriction of rabbit ductus arteriosus occurs via inhibition of a 4-aminopyridine-, voltage-sensitive potassium channel'. Together they form a unique fingerprint.

Cite this