Oxygen sensing in the rabbit ductus arteriosus occurs via inhibition of a KDR channel

H. L. Reeve, M. Tristani-Firouzi, E. K. Weir, S. L. Archer

Research output: Contribution to journalArticlepeer-review

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Abstract

The ductus arteriosus (DA) is a vital fetal structure which closes at birth, primarily in response to an increase in oxygen (O1) tension. The mechanism of the O2-induced constriction of the DA remains uncertain. In the pulmonary artery, hypoxic vasoconstriction occurs via inhibition of a K+ channel. We therefore tested the hypothesis that O2 causes DA constriction by inhibiting K+ channels. In isolated DA rings from late-geslation fetal rabbits, increasing O2 levels from 20 to 130 Torr caused rapid and reversible constriction. Rings also constricted to low dose 4-aminopyridine (4-AP, 1-lOmM; n=13; selective for the delayed rectifier (KDR) K+ channel) but not to the Ca2+-dependent K+ channel blocker tetraethylammonium (1-IOmM; n=9) or the ATP-dependent K+ channel blocker, glibenclamide (1μM; n=13). Amphotericin-perforated patch-clamp studies, using freshly dispersed DA smooth muscle cells, showed that whole-cell, 4-AP-sensitive K+ channel currents were reversibly inhibited by increasing O2 from 20 to 130 Torr. In current-clamp, cells were depolarized by increasing O2 levels or by exposing the cell to lmM4-AP. These data suggest that O2-induced DA constriction may be initialed by the inhibition of a 4-AP-sensitive K+ channel of the KDR type.

Original languageEnglish (US)
Pages (from-to)A581
JournalFASEB Journal
Volume10
Issue number3
StatePublished - Dec 1 1996

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