Normobaric CO₂ and hyperbaric O₂ stimulate the same neurons in the solitary complex

We recently reported that neurons in the dorsocaudal chemosensitive area, the solitary complex (SC), are stimulated by reactive oxygen species (ROS) during acute hyperbaric oxygen (HBO₂), suggesting that oxidative stress modulates cardiorespiratory networks [1,2]. Hyperoxia is known to have various effects on car-diorespiratory function [3,4], and it has been proposed that central hypoventilation syndromes, for example, SIDS, are due in part to increased oxidative stress of neurons after birth [5]. Thus, we have tested the hypothesis that excitability of CO₂-chemosensitive neurons in the caudal SC is altered during oxidative stress at normobaric and hyperbaric pressures.

Intracellular recordings were made from SC neurons in 300 μm thick medullary slices prepared from weaned and adult rats. Control medium was equilibrated with 95% O₂ -5% CO₂ at barometric pressure (P_B) ~1 atmosphere absolute (ATA) (medium PO₂ ~720 Torr, PCO₂ ~38 Torr). A slice was maintained in a hyperbaric chamber and exposed to one or more of the following conditions (~37°C): 1)normobaric hypercapnia (8–20 mins 15% CO₂ in O₂) to test for CO₂ chemosensitivity; 2)normocapnic HBO₂ (10–20 mins 98.3% O₂ -1.65% CO₂ at P_B 3.3 ATA) and 3)pro-oxidants at P_B ~1ATA (8–10 mins 500 μM Chloramine-T or 1 mM N-chlorosuccinimide) to test for the effects of ROS; and 4)hypercapnic HBO₂ (10–20 mins 95% O₂ -5% CO₂ at P_B 3.2ATA) to test for the effects of hypercapnic acidosis on sensitivity to HBO₂[6,7,9]. During HBO₂, tissue PO₂ (mean ± S.E.) at the core of the slice (150 μm depth) increased from 291 ± 20 to 1517 ± 15 Torr [6].

Focusing on the caudal SC, 62% (18/29) of the neurons tested were depolarized by normobaric hypercapnia. Of these, 78% (14/18) were stimulated by normocapnic HBO₂ and pro-oxidants. When hypercapnia and HBO₂ were combined (hypercapnic HBO₂), the firing rate response was greater to both stimuli than to the sum of their individual responses. Most neurons (9/11) that were CO₂ insensitive were also unresponsive to HBO₂ and/or pro-oxidants.

We conclude that acute exposure to oxidative stress, either by increased tissue PO₂ at hyperbaric pressure or pro-oxidants at normobaric pressure, stimulates CO₂-chemosensitive neurons in the SC, suggesting that central chemosensitivity may likewise be affected by oxidative stress. It is unclear, however, if the strong neuronal excitation observed when hypercapnic acidosis and HBO₂ are combined is due to increased lipid peroxidation during intracellular acidosis [7,8,9] or to the effect of increased ROS on CO₂ chemosensitivity.