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 (K2p) K+ channels. Such background K+ channels contribute to the maintenance of resting membrane potential in cells where they are expressed and ascription of specific K2p 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 K2p channels has not been robustly investigated other than by demonstration immunohistochemically of the TASK2 protein (Kemp et al. 2003).
KeywordsCarotid Body Hypoxic Pulmonary Vasoconstriction Pulmonary Artery Smooth Muscle Cell Neuroepithelial Body Arterial Chemoreceptor
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