Chemical oxidants acidify solitary complex (SC) neurons in the rat.

Breathing high levels of oxygen (i.e. hyperoxia) causes hyperventilation and unstable breathing in normal and carotid-deafferented animals (1,2). Prolonged exposure to hyperoxia can disrupt central nervous system (CNS) function and result in a condition termed CNS O2 toxicity, the primary sign of which is convulsion (3,4). The mechanism by which hyperoxia stimulates ventilation and disrupts CNS function is unknown; however, these effects are thought to result from increased production of reactive oxygen species (ROS) during hyperoxia and subsequent oxidation of cellular components vital to normal function (4,5). At moderate levels, ROS, including superoxide and nitric oxide, as well as their reactive nonradical derivatives (e.g. peroxide, S-nitrosothiols), modulate many physiological processes (4,6), including the hypoxic ventilatory response (7). However, at higher concentrations, ROS can result in oxidative stress that damages cellular components and therefore, are toxic to most cells (4,6). For example, ROS have been implicated in central respiratory control disorders, such as central alveolar hypoventilation syndrome (e.g. sudden infant death syndrome) (8). We have studied the electrophysiological effects of oxidative stress imposed by hyperoxia or by chemical oxidants on neurons from the dorsal medulla oblongata (9-11). In particular, we have studied the nucleus tractus solitarius and dorsal motor nucleus (i.e. solitary complex, SC). We showed that acute exposure to hyperoxia or chemical oxidants selectively stimulated firing rate of CO2/H-chemosensitive SC neurons (4,11). The SC is an important cardio-respiratory control center and CO2/H-chemosensitive neurons are thought to provide the primary stimulus for breathing (12). Therefore, our results may explain how oxidative stress causes hyperventilation, and with chronic exposure, possibly contributes to central cardiorespiratory control dysfunction. In addition, we showed that the antioxidant Trolox-C blocked the effects of hyperoxia, but not of hypercapnia, on neuronal excitability, thus suggesting that hyperoxia effects neuronal excitability by a ROS-dependent mechanism (11). We also showed