Hemoxygenase-2 Is an Oxygen Sensor for a Calcium-Sensitive Potassium Channel-Reference-Cited by-同舟云学术

Hemoxygenase-2 Is an Oxygen Sensor for a Calcium-Sensitive Potassium Channel

Published:2004-12-17 Issue:5704 Volume:306 Page:2093-2097
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Williams Sandile E. J.¹²³⁴⁵,Wootton Phillippa¹²³⁴⁵,Mason Helen S.¹²³⁴⁵,Bould Jonathan¹²³⁴⁵,Iles David E.¹²³⁴⁵,Riccardi Daniela¹²³⁴⁵,Peers Chris¹²³⁴⁵,Kemp Paul J.¹²³⁴⁵

Affiliation:

1. School of Biomedical Sciences, University of Leeds, Leeds LS2 9JT, UK.

2. School of Chemistry, University of Leeds, Leeds LS2 9JT, UK.

3. School of Biology, University of Leeds, Leeds LS2 9JT, UK.

4. School of Medicine, University of Leeds, Leeds LS2 9JT, UK.

5. Cardiff School of Biosciences, Museum Avenue, Cardiff University, Cardiff, CF10 3US, UK.

Abstract

Modulation of calcium-sensitive potassium (BK) channels by oxygen is important in several mammalian tissues, and in the carotid body it is crucial to respiratory control. However, the identity of the oxygen sensor remains unknown. We demonstrate that hemoxygenase-2 (HO-2) is part of the BK channel complex and enhances channel activity in normoxia. Knockdown of HO-2 expression reduced channel activity, and carbon monoxide, a product of HO-2 activity, rescued this loss of function. Inhibition of BK channels by hypoxia was dependent on HO-2 expression and was augmented by HO-2 stimulation. Furthermore, carotid body cells demonstrated HO-2–dependent hypoxic BK channel inhibition, which indicates that HO-2 is an oxygen sensor that controls channel activity during oxygen deprivation.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference24 articles.

1. Hypoxic suppression of K+ currents in type I carotid body cells: Selective effect on the Ca2+-activated K+ current

2. O 2 Modulates Large-Conductance Ca 2+ -Dependent K + Channels of Rat Chemoreceptor Cells by a Membrane-Restricted and CO-Sensitive Mechanism

3. Oxygen causes fetal pulmonary vasodilation through activation of a calcium-dependent potassium channel.

4. Role of a Novel KCaOpener in Regulating K+Channels of Hypoxic Human Pulmonary Vascular Cells

5. Anoxia differentially modulates multiple K+currents and depolarizes neonatal rat adrenal chromaffin cells

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