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. (C) 2004 Elsevier Ltd. All rights reserved.