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

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 c...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2004-12, Vol.306 (5704), p.2093-2097
Main Authors: Williams, Sandile E. J, Wootton, Phillippa, Mason, Helen S, Bould, Jonathan, Iles, David E, Riccardi, Daniela, Peers, Chris, Kemp, Paul J
Format: Article
Language:English
Subjects:
Anatomy
Animals
Antibodies
Biological and medical sciences
Carbon Monoxide - metabolism
Carotid body
Carotid Body - cytology
Carotid Body - physiology
Cell Hypoxia
Cell Line
Cell membranes. Ionic channels. Membrane pores
Cell structures and functions
Donors
Fundamental and applied biological sciences. Psychology
HEK293 cells
Heme - metabolism
Heme Oxygenase (Decyclizing) - genetics
Heme Oxygenase (Decyclizing) - metabolism
Human biology
Humans
Hypoxia
Immunoprecipitation
Inhibition
Ion channels
Large conductance calcium activated potassium channels
Large-Conductance Calcium-Activated Potassium Channel alpha Subunits
Mammals
Membrane Potentials
Molecular and cellular biology
NADP - metabolism
Neurons
Oxygen
Oxygen - physiology
Patch-Clamp Techniques
Potassium
Potassium Channels, Calcium-Activated
Proteins
Pumps
Rats
Ribonucleic acid
RNA
RNA Interference
RNA, Small Interfering - pharmacology
Scientific Concepts
Sensors
Small interfering RNA
Statistical Analysis
Tissues
Transfection
Ventilation
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Description
Summary: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.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.1105010