About this Biochemistry, Genetics and Molecular Biology article

O2 sensing in the human ductus arteriosus: redox-sensitive K+ channels are regulated by mitochondria-derived hydrogen peroxide by S. L. Archer; X.-C. Wu; B. Thébaud; R. Moudgil; K. Hashimoto; E.D. Michelakis is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

The ductus arteriosus (DA) is a fetal artery that allows blood ejected from the right ventricle to bypass the pulmonary circulation in utero. At birth, functional closure of the DA is initiated by an O 2 -induced, vasoconstrictor mechanism which, though modulated by endothelialderived endothelin and prostaglandins, is intrinsic to the smooth muscle cell (DASMC) wMichelakis et al., Circ. Res. 91 (2002); pp. 478-486x. As pO 2 increases, a mitochondrial O 2 -sensor (electron transport chain complexes I or III) is activated, which generates a diffusible redox mediator (H 2 O 2 ). H 2 O 2 inhibits voltage-gated K q channels (Kv) in DASMC. The resulting membrane depolarization activates L-type Ca 2q channels, thereby promoting vasoconstriction. Conversely, inhibiting mitochondrial ETC complexes I or III mimics hypoxia, depolarizing mitochondria, and decreasing H 2 O 2 levels. The resulting increase in K q current hyperpolarizes the DASMC and relaxes the DA. We have developed two models for study of the DA's O 2 -sensor pathway, both characterized by decreased O 2 -constriction and Kv expression: (i) preterm rabbit DA, (ii) ionically-remodeled, human term DA. The O 2 -sensitive channels K

Author

S. L. Archer; X.-C. Wu; B. Thébaud; R. Moudgil; K. Hashimoto; E.D. Michelakis

Publisher

Walter de Gruyter GmbH

Published

2004

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)