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Originally published in Science Express on 4 November 2004
Science 17 December 2004:
Vol. 306. no. 5704, pp. 2093 - 2097
DOI: 10.1126/science.1105010
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Reports

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

Sandile E. J. Williams,1,5 Phillippa Wootton,1 Helen S. Mason,1,5 Jonathan Bould,2 David E. Iles,3 Daniela Riccardi,5 Chris Peers,4 Paul J. Kemp1,5*

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.

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.

* To whom correspondence should be addressed. E-mail: KempPJ{at}Cardiff.ac.uk

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