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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Veröffentlicht in:	Science (American Association for the Advancement of Science) 2004-12, Vol.306 (5704), p.2093-2097
Hauptverfasser:	Williams, Sandile E. J, Wootton, Phillippa, Mason, Helen S, Bould, Jonathan, Iles, David E, Riccardi, Daniela, Peers, Chris, Kemp, Paul J
Format:	Artikel
Sprache:	eng
Schlagworte:	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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Zusammenfassung:	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