| Breathing oxygen at greater than room pressure (∼1 atmosphere absolute; ATA), i.e. hyperbaric oxygen (HBO2), causes hyperventilation. The mechanism by which HBO2 affects cardiorespiratory control is unknown, but thought to result from the effects of free radicals on putative CO2-chemoreceptor neurons of the cardiorespiratory system. Neither the effects of hyperoxia or increased pressure (i.e. the two components of HBO2) on excitability of neurons in a respiratory control area have been described. Therefore, a technique was developed for making sharp electrode intracellular recordings from neurons in the solitary complex (SC: nucleus tractus solitarius, dorsal motor nucleus), an important cardiorespiratory control region of the brainstem, in rat brain slices while independently increasing oxygen tension or barometric pressure. The hypothesis that HBO2 selectively stimulates CO2-sensitive SC neurons by a free-radical dependent mechanism was tested. Compression to 2--4 ATA helium stimulated 32 of 102 (31%) SC neurons, typically with decreased input resistance, possibly by increasing cationic conductance. At 3 ATA helium, exposure to HBO2 increased firing rate and input resistance in 43 of 113 (38%) SC neurons tested, possibly by decreasing K+ channel conductance. Neuronal responses to HBO2 were reversible, mimicked by chemical oxidants and blocked with an antioxidant, suggesting the stimulation was mediated by free radicals. Hypercapnia (high CO2 ) increased firing rate in 32 of 60 (53%) cells tested. Of the CO 2-sensitive neurons, 81% (26/32) were also stimulated by HBO2, whereas 89% (25/28) of CO2-insensitive cells were HBO2-insensitive, thus indicating a strong relationship between CO2- and HBO2-sensitivity of SC neurons. Further the response to CO2 was not blocked by an antioxidant. These findings suggest: (i) HBO2 stimulates SC neurons by a free radical-dependent mechanism; (ii) CO2-sensitive, but not CO2-insensitive, neurons are also HBO2-sensitive; (iii) CO2-sensitivity is not dependent on free radicals; (iv) hyperbaric pressure (2--4 ATA) stimulates some SC neurons. Given that central CO2-chemoreceptors provide the primary stimulus for breathing, selective stimulation of central CO 2-sensitive neurons by HBO2 may explain hyperoxic hyperventilation and suggest a mechanism by which oxidative stress contributes to cardiorespiratory control disorders. These results may provide insight into how oxidative stress affects neuronal excitability in general. |
