Hyperbaric oxygen and chemical oxidants stimulate CO sub(2)/H super(+)-sensitive neurons in rat brain stem slices

Hyperoxia, a model of oxidative stress, can disrupt brain stem function, presumably by an increase in O sub(2) free radicals. Breathing hyperbaric oxygen (HBO sub(2)) initially causes hyperoxic hyperventilation, whereas extended exposure to HBO sub(2) disrupts cardiorespiratory control. Presently, it is unknown how hyperoxia affects brain stem neurons. We have tested the hypothesis that hyperoxia increases excitability of neurons of the solitary complex neurons, which is an important region for cardiorespiratory control and central CO sub(2)/H super(+) chemoreception. Intracellular recordings were made in rat medullary slices during exposure to 2-3 atm of HBO sub(2), HBO sub(2) plus antioxidant (Trolox C), and chemical oxidants (N-chlorosuccinimide, chloramine-T). HBO sub(2) increased input resistance and stimulated firing rate in 38% of neurons; both effects of HBO sub(2) were blocked by antioxidant and mimicked by chemical oxidants. Hypercapnia stimulated 32 of 60 (53%) neurons. Remarkably, these CO sub(2)/H super(+)-chemosensitive neurons were preferentially sensitive to HBO sub(2); 90% of neurons sensitive to HBO sub(2) and/or chemical oxidants were also CO sub(2)/H super(+) chemosensitive. Conversely, only 19% of HBO sub(2)-insensitive neurons were CO sub(2)/H super(+) chemosensitive. We conclude that hyperoxia decreases membrane conductance and stimulates firing of putative central CO sub(2)/H super(+)-chemoreceptor neurons by an O sub(2) free radical mechanism. These findings may explain why hyperoxia, paradoxically, stimulates ventilation.