Oxygen sensing by human recombinant tandem-P domain potassium channels

Oxygen sensing in many tissues is crucially dependent upon hypoxia-evoked suppression of K⁺ channel activity (Kemp et al. 2003; Lopez-Barneo et al. 2001; Peers, 1997; Patel and Honore, 2001; Peers & Kemp, 2001). This is particularly true of the prospective airway O₂ sensor, the neuroepithelial body of the lung (Youngson et al. 1993; Cutz and Jackson, 1999), their immortalised cellular counterpart (HI46 cells - O’Kelly et al. 1998; O’Kelly et al. 2000b; O’Kelly et al. 2000a; Hartness et al. 2001; O’Kelly et al. 1999; Kemp et al. 2003) and the arterial O2 sensor, the carotid body (Lopez-Barneo et al. 1988; Peers, 1990; Buckler, 1997). In addition, the K⁺ channels almost certainly contribute to hypoxic vasoconstriction of the pulmonary vasculature (Post et al. 1992; Weir & Archer, 1995; Osipenko et al. 2000 Coppock et al. 2001;) although the full extent and nature of their involvement is still somewhat controversial (Ward & Aaronson, 1999). Although each tissue and model system expresses a cell-specific gamut of K⁺ channels, central to O₂ sensory transduction in several is hypoxic inhibition of members of the gene family encoding tandem P- domain (K_2p) K⁺ channels. Such background K⁺ channels contribute to the maintenance of resting membrane potential in cells where they are expressed and ascription of specific K_2p channels to cellular hypoxic responses have been shown directly in the airway chemosensing model H146 cells (Hartness et al. 2001) - TASK3) and inferred in carotid body glomus cells (Buckler et al. 2000) - TASK1) and arteriolar smooth muscle of the pulmonary circulation(Gurney et al. 2002) - TASK1 or TASK3). The current exception to this potentially unifying theme in acute O₂ sensing is the native neuroepithelial body, where involvement of K_2p channels has not been robustly investigated other than by demonstration immunohistochemically of the TASK2 protein (Kemp et al. 2003).