O2 sensing in the human ductus arteriosus: redox-sensitive K+ channels are regulated by mitochondria-derived hydrogen peroxide
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| 024 | 7 | 0 | |a 10.1515/BC.2004.014 |2 doi |
| 035 | |a (NATIONALLICENCE)gruyter-10.1515/BC.2004.014 | ||
| 245 | 0 | 0 | |a O2 sensing in the human ductus arteriosus: redox-sensitive K+ channels are regulated by mitochondria-derived hydrogen peroxide |h [Elektronische Daten] |c [S. L. Archer, X.-C. Wu, B. Thébaud, R. Moudgil, K. Hashimoto, E.D. Michelakis] |
| 520 | 3 | |a 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 O2-induced, vasoconstrictor mechanism which, though modulated by endothelialderived endothelin and prostaglandins, is intrinsic to the smooth muscle cell (DASMC) [Michelakis et al., Circ. Res. 91 (2002); pp. 478-486]. As pO2 increases, a mitochondrial O2-sensor (electron transport chain complexes I or III) is activated, which generates a diffusible redox mediator (H2O2). H2O2 inhibits voltagegated K+ channels (Kv) in DASMC. The resulting membrane depolarization activates Ltype Ca2+ channels, thereby promoting vasoconstriction. Conversely, inhibiting mitochondrial ETC complexes I or III mimics hypoxia, depolarizing mitochondria, and decreasing H2O2 levels. The resulting increase in K+ current hyperpolarizes the DASMC and relaxes the DA. We have developed two models for study of the DAs O2-sensor pathway, both characterized by decreased O2-constriction and Kv expression: (i) preterm rabbit DA, (ii) ionicallyremodeled, human term DA. The O2-sensitive channels Kv1.5 and Kv2.1 are important to DA O2-constriction and overexpression of either channel enhances DA constriction in these models. Understanding this O2-sensing pathway offers therapeutic targets to modulate the tone and patency of human DA in vivo, thereby addressing a common form of congenital heart disease in preterm infants. | |
| 540 | |a Copyright © 2004 by Walter de Gruyter GmbH & Co. KG | ||
| 690 | 7 | |a Biochemistry |2 nationallicence | |
| 690 | 7 | |a Molecular biology |2 nationallicence | |
| 690 | 7 | |a Cellular biology |2 nationallicence | |
| 700 | 1 | |a Archer |D S. L. |4 aut | |
| 700 | 1 | |a Wu |D X.-C |4 aut | |
| 700 | 1 | |a Thébaud |D B. |4 aut | |
| 700 | 1 | |a Moudgil |D R. |4 aut | |
| 700 | 1 | |a Hashimoto |D K. |4 aut | |
| 700 | 1 | |a Michelakis |D E.D. |4 aut | |
| 773 | 0 | |t Biological Chemistry |d Walter de Gruyter |g 385/3-4(2004-04-13), 205-216 |x 1431-6730 |q 385:3-4<205 |1 2004 |2 385 |o bchm | |
| 856 | 4 | 0 | |u https://doi.org/10.1515/BC.2004.014 |q text/html |z Onlinezugriff via DOI |
| 908 | |D 1 |a research article |2 jats | ||
| 950 | |B NATIONALLICENCE |P 856 |E 40 |u https://doi.org/10.1515/BC.2004.014 |q text/html |z Onlinezugriff via DOI | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Archer |D S. L. |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Wu |D X.-C |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Thébaud |D B. |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Moudgil |D R. |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Hashimoto |D K. |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Michelakis |D E.D. |4 aut | ||
| 950 | |B NATIONALLICENCE |P 773 |E 0- |t Biological Chemistry |d Walter de Gruyter |g 385/3-4(2004-04-13), 205-216 |x 1431-6730 |q 385:3-4<205 |1 2004 |2 385 |o bchm | ||
| 900 | 7 | |b CC0 |u http://creativecommons.org/publicdomain/zero/1.0 |2 nationallicence | |
| 898 | |a BK010053 |b XK010053 |c XK010000 | ||
| 949 | |B NATIONALLICENCE |F NATIONALLICENCE |b NL-gruyter | ||