Science (New York, N.Y.) · 2004
Hemoxygenase-2 is an oxygen sensor for a calcium-sensitive potassium channel.
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Williams Sandile E J, Wootton Phillippa, Mason Helen S, Bould Jonathan, Iles David E, Riccardi Daniela, Peers Chris, Kemp Paul J
Аннотация
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.
Предметные рубрики MeSH
AnimalsCarbon MonoxideCarotid BodyCell HypoxiaCell LineHemeHeme Oxygenase (Decyclizing)HumansImmunoprecipitationLarge-Conductance Calcium-Activated Potassium Channel alpha SubunitsLarge-Conductance Calcium-Activated Potassium ChannelsMembrane PotentialsNADPOxygenPatch-Clamp TechniquesPotassium Channels, Calcium-ActivatedRNA InterferenceRNA, Small InterferingRatsTransfection