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

Individuals suffering from a variety of cardiorespiratory diseases which are characterised by sustained or intermittent chronic hypoxia - such as chronic obstructive pulmonary disease, sleep apnoea, emphysema, congestive heart failure and stroke - often undergo pathological adaptation of tissue responses to acute hypoxia. Such a notion is supported experimentally by observations in chemosensing tissues such as the pulmonary vasculature, where voltage-gated K+ channel expression is selectively suppressed in chronic hypoxia (Smirnov et al 1994) and carotid body, where chronic hypoxia both in vitro (Stea et al 1992; Stea et al. 1995), and in vivo (Wyatt et al 1995; Eden & Hanson, 1987a; Eden & Hanson, 1987b) has been shown to modulate the acute cellular and whole-body hypoxic responses. Thus, it seems likely that remodelling of ion channel functional activity by sustained or intermittent episodes of hypoxia may underlie the responses to certain pathologies such as pulmonary hypertension (for recent reviews see Prabhakar, 2001; Prabhakar, 2002; Lanfranchi & Somers, 2001) in addition to the well documented adaptation to high altitude (Monge & Leon-Velarde, 1991)