Normobaric CO2 and hyperbaric O2 stimulate the same neurons in the solitary complex
Respiratory Research volume 2, Article number: 6.6 (2001)
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 . 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 (PB) ~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 PB 3.3 ATA) and 3)pro-oxidants at PB ~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 PB 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 .
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.
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Many thanks to DK Mulkey, and RA Henderson III. Research supported by ONR N000140110179, NIH R01 HL 56683, and WSU-SOM/Kettering Foundation.
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Dean, J. Normobaric CO2 and hyperbaric O2 stimulate the same neurons in the solitary complex. Respir Res 2 (Suppl 1), 6.6 (2001). https://doi.org/10.1186/rr124