Sodium/Proton exchanger 3 in the medulla oblongata and set point of breathing control.
BACKGROUND
In vivo inhibition of the sodium/proton exchanger 3 (NHE3) in chemosensitive neurons of the ventrolateral brainstem augments central respiratory drive in anesthetized rabbits.


OBJECTIVE
To further explore the possible role of this exchanger for the control of breathing, we examined the individual relationship between brainstem NHE3 abundance and ventilation in rabbits during wakefulness.


METHODS
In 32 adult male rabbits on standard nutritional alkali load, alveolar ventilation, metabolic CO2 production, and blood gases were determined, together with arterial and urinary acid-base status and renal base control functions. Expression of NHE3 in brainstem tissue from the obex region was determined by quantitative real-time reverse-transcription polymerase chain reaction analysis.


RESULTS
Regarding the distribution above and below the median, we classified high and low brainstem NHE3 animals, expressing a mean (+/- SEM) NHE3 mRNA of 2.08 +/- 0.28 and 0.72 +/- 0.06 fg cDNA/mg RNA, respectively. Alveolar ventilation of high brainstem NHE3 animals was lower than that of low brainstem NHE3 animals (715 +/- 36 vs. 919 +/- 41 ml . minute(-1); p < 0.01), a finding also reflected by a marked difference in Pa(CO2) (5.24 +/- 0.16 vs. 4.44 +/- 0.15 kPa; p < 0.01). Among possible secondary factors, CO2 production, systemic base excess, and fractional renal base reabsorption were not found to be different.


CONCLUSIONS
We conclude that the level of brainstem NHE3 expression-most likely via intracellular pH modulation-contributes to the individual control of breathing and Pa(CO2) in conscious rabbits by adjusting the set point and the loop gain of the system.
Wiemann
Martin
M
Department of Physiology, University of Duisburg-Essen, 45122 Essen, Germany. martin.wiemann@uni-essen.de
Frede
Stilla
S
Bingmann
Dieter
D
Kiwull
Peter
P
Kiwull-Schöne
Heidrun
H
D000042:Absorption; D000818:Animals; D001158:Arteries; D001639:Bicarbonates / Q000378:metabolism; D001933:Brain Stem / Q000378:metabolism; D002245:Carbon Dioxide / Q000097:blood; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism*; D010313:Partial Pressure; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D015656:Respiratory Mechanics; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics / Q000378:metabolism*
D001639:Bicarbonates; D012333:RNA, Messenger; C000613385:SLC9A3 protein, human; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D002245:Carbon Dioxide