Modification of the Glutathione Redox Environment and Chemoreceptor Cell Responses

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Carotid body (CB) chemoreceptor cells (CBCC) are involved in maintaining the homeostasis of O2 by detecting arterial blood PO2 and become activated when arterial PO2 decreases. In response to hypoxia, CBCC release neurotransmitters which excite the adjacent afferent nerve terminals of the carotid sinus nerve, increase their action potential and, via the central projections of the nerve to the brain stem, activate ventilation. The proposed cascade of transduction of hypoxia requires the presence of an oxygen sensor that is coupled to specific K channels. The decrease in the opening probability of these, leads to CBCC depolarization followed by Ca entry via voltagedependent Ca channels and consequently, the release of excitatory transmitters (5).However, the molecular identity of the O2 sensor and the mechanism coupling the oxygen sensor to the exocytotic machinery has thus far remained unclear. Reactive oxygen species (ROS) have been proposed as mediators, either triggers or modulators, of the hypoxic responses in specialized O2-sensing cell types including CBCC, erythropoietin producing cells and pulmonary artery smooth muscle cells (6). The superoxide radical, O2 , is quantitatively the most relevant primary ROS, capable of reacting with many molecules to generate altered structures and new secondary ROS. One of the major sources of ROS is the mitochondrial respiratory chain, where univalent reduction of O2 may take place in some steps of the overall transport system. There are two places where the superoxide radical can be produced: the complex I NADPH-Coenzyme Q Oxido-Reductase and the ubiquinone pool. In both places there are electron shuttle molecules (flavin adenin mononucleotide and ubiquinone) that can accept electrons. When they accept a single electron they become free radical molecules themselves, capable of slipping the electron to molecular O2. The mitochondrial respiratory chain is also the main place of ATP synthesis. Two hypotheses postulate that ROS participate in the control of the CBCC activity. The first hypothesis developed by Acker and colleagues (3)