Ion channel regulation by chronic hypoxia in models of acute oxygen sensing

Several potentially life-threatening cardiovascular and respiratory disorders result in prolonged deprivation of oxygen, which in turn results in significant cellular adaptation, or remodelling. An important component of this functional adaptation arises as a direct consequence of altered ion channel expression by chronic hypoxia. In this review, we discuss current understanding of this hypoxic remodelling process, with particular reference to regulation of L-type Ca2+ channels and high-conductance, Ca2+-sensitive K+ (BK) channels. In systems where this remodelling occurs, changes in functional expression of these particular channels evokes marked alteration in, or responses to, Ca2+-dependent events. Evidence to date indicates that channel expression can be modulated at the transcriptional level but, additionally, that crucial post-transcriptional events are also regulated by chronic hypoxia. Importantly, such remodelling is, in some cases, strongly associated with production of amyloid peptides of Alzheimer's disease, implicating chronic hypoxia as a causative factor in the progression of specific pathology. Moreover, subtle changes in functional expression of BK channels implicates chronic hypoxia as an important regulator of cell excitability.