Oxygen sensing by human recombinant large conductance, calcium-activated potassium channels: regulation by acute hypoxia

Although O₂-sensitive tissues express a wide variety of channel types (Lopez-Barneo et al. 2001; Peers & Kemp, 2001), central to the cellular mechanism of O₂ sensing in many is hypoxic suppression of large conductance Ca²⁺-activated K⁺ channels (maxiK, BKCa or Slo channels). Thus, hypoxic inhibition of maxiK channels has been demonstrated in carotid body (Peers, 1990; Pardal et al. 2000; Riesco-Fagundo et al. 2001), pulmonary smooth muscle (Cornfield et al. 1996), chromaffin cells (Thompson & Nurse, 1998), and other non-chemosensory tissues such as central neurones (Liu et al. 1999; Jiang & Haddad, 1994b). Contribution of this channel type to carotid body, chromatin cell and central neuronal function is well supported although some controversy still surrounds their involvement in pulmonary vasoconstriction (Ward & Aaronson, 1999) where there is also good evidence for both delayed rectifier (Tristani-Firouzi et al. 1996) and tandem P domain K⁺ channels in the response (Gurney et al. 2002); the later observation is fully supported by our recent report of O₂ sensitivity of the tandem P domain channel, hTASKl, in a recombinant mammalian system similar to that employed in the present study (Lewis et al., 2001).