Acute Oxygen Sensing in Heme Oxygenase-2 Null Mice

Hemeoxygenase-2 (HO-2) is an antioxidant enzyme that can modulate recombinant maxi-K⁺ channels and has been proposed to be the acute O₂ sensor in the carotid body (CB). We have tested the physiological contribution of this enzyme to O₂ sensing using HO-2 null mice. HO-2 deficiency leads to a CB phenotype characterized by organ growth and alteration in the expression of stress-dependent genes, including the maxi-K⁺ channel α-subunit. However, sensitivity to hypoxia of CB is remarkably similar in HO-2 null animals and their control littermates. Moreover, the response to hypoxia in mouse and rat CB cells was maintained after blockade of maxi-K⁺ channels with iberiotoxin. Hypoxia responsiveness of the adrenal medulla (AM) (another acutely responding O₂-sensitive organ) was also unaltered by HO-2 deficiency. Our data suggest that redox disregulation resulting from HO-2 deficiency affects maxi-K⁺ channel gene expression but it does not alter the intrinsic O₂ sensitivity of CB or AM cells. Therefore, HO-2 is not a universally used acute O₂ sensor.