Hemoxygenase-2 Is an Oxygen Sensor for a Calcium-Sensitive Potassium Channel
Copyright policy )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 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.
- University of Leeds United Kingdom
- Cardiff University United Kingdom
Carbon Monoxide, Carotid Body, Patch-Clamp Techniques, Heme, Transfection, Cell Hypoxia, Cell Line, Membrane Potentials, Rats, Oxygen, Potassium Channels, Calcium-Activated, Heme Oxygenase (Decyclizing), Animals, Humans, Immunoprecipitation, RNA Interference, Large-Conductance Calcium-Activated Potassium Channels, RNA, Small Interfering, Large-Conductance Calcium-Activated Potassium Channel alpha Subunits, NADP
Carbon Monoxide, Carotid Body, Patch-Clamp Techniques, Heme, Transfection, Cell Hypoxia, Cell Line, Membrane Potentials, Rats, Oxygen, Potassium Channels, Calcium-Activated, Heme Oxygenase (Decyclizing), Animals, Humans, Immunoprecipitation, RNA Interference, Large-Conductance Calcium-Activated Potassium Channels, RNA, Small Interfering, Large-Conductance Calcium-Activated Potassium Channel alpha Subunits, NADP
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