O-2-sensing mechanisms in excitable cells: Role of plasma membrane K+ channels

Although carotid chemosensitive glomus cells have been the most extensively studied from the vantage point of how cells sense the lack of O-2, it is clear that all tissues sense O-2 deprivation. In addition, all mammalian cells can trigger a cascade of events that, depending on the severity and duration of hypoxia-induced stress, can lead to permanent injury and death or to adaptation and survival. Crucial in this cascade, we believe, how the cascade is initiated, how O-2 lack is detected by cells, and how these initial steps can activate further processes. In this chapter, we focus on the initial steps of O-2 sensing in tissues most commonly studied, i.e. carotid glomus cells, central neurons, smooth muscle cells, and neuro-epithelial bodies of the airways. Recently it has become clear that plasma membranes of various tissues can sense the lack of O-2, not only indirectly via alterations in the intracellular milieu (such as pH, Ca, ATP, etc), but also directly through an unknown mechanism that involves plasma-membrane K channels and possibly other membrane proteins. This latter mechanism is suspected to be totally independent of cytosolic changes because excised patches from plasma membranes were used in these experiments from carotid cells and neurons. There are a number of questions in this exciting area of research that pertain to the role of this plasma-membrane O-2-sensing mechanism in the overall cell response, identification of all the important steps in O-2 sensing, differences between O-2-tolerant and O-2-susceptible cells, and differences between acute and chronic cell responses to lack of O-2.