Acute oxygen sensing in cellular models: Relevance to the physiology of pulmonary neuroepithelial and carotid bodies

Abstract

The combination of studies in native tissues and immortalised model systems during the last decade has made possible a deeper understanding of the physiology and functional morphology of arterial and airway oxygen sensors. Complementary and overlapping information from these earlier studies has allowed a detailed description of the cellular events that link decreased environmental oxygen to the release of physiologically important vasoactive transmitters. Since these basic pathways have now been defined functionally, what remains to be determined is the molecular identity of the specific proteins involved in the signal transduction pathways, and how these proteins interact to produce a full physiological response. With these goals clearly in sight, we have embarked upon a strategy that is a novel combination of proteomics and functional genomics. It is hoped this strategy will enable us to develop and refine the initial models in order to understand more completely the process of oxygen sensing in health and disease. Anat Rec Part A 270A: 41-50, 2003.

Molecular diversity and function of K+ channels in airway and alveolar epithelial cells

“…It should be noted that the large-conductance Ca 2ϩ -activated (BKCa) channel, commonly associated with the 6-TMD family, could be composed of 7 TMD. line), have been shown to be inhibited after acute hypoxia (35,36,87 (63). Moreover, it has been shown that Kv1.1, Kv4.3, and Kv9.3 mRNA expression is decreased after chronic hypoxia in VSMC (63).…”

“…Lung ability to rapidly adapt to environmental changes in PO 2 is crucial for survival. Neuroepithelial bodies (NEB) localized in the airway epithelium, arterial carotid bodies, and pulmonary smooth muscle cells are the three main PO 2 -sensing systems (35,36). These cells express several ion channels, particularly K ϩ channels that are sensitive to O 2 levels.…”

Molecular Background of Leak K+Currents: Two-Pore Domain Potassium Channels

“…In contrast to acidosis, hypoxia-induced inhibition of TASK channels depends on cellular integrity (38) and the cell type in which the channel is expressed [e.g., it is absent in Xenopus oocytes (267), but operates in HEK cells (156,196)]. Several indirect mechanisms have been proposed by which hypoxia influences the activity of oxygen-sensitive potassium channels.…”

Polymodal regulation of hTREK1 by pH, arachidonic acid, and hypoxia: physiological impact in acidosis and alkalosis

“…These recent data emphasize two important points: first, hTREK1 is the latest addition to the steadily increasing array of O 2 -sensitive ion channels (see Refs. 8,11,21), and second, where such channels are expressed in the CNS, it is of paramount importance to study their regulation at physiologically pertinent PO 2 levels (6).…”