Published ahead of print on June 9, 2005, doi:10.1164/rccm.200411-1567OC
© 2005 American Thoracic Society doi: 10.1164/rccm.200411-1567OC
Sodium/Proton Exchanger 3 in the Medulla Oblongata and Set Point of Breathing ControlDepartment of Physiology, University of Duisburg-Essen, Essen; and Department of Physiology, Ruhr University, Bochum, Germany Correspondence and requests for reprints should be addressed to Dr. Martin Wiemann, Department of Physiology, University of Duisburg-Essen, 45122 Essen, Germany. E-mail: martin.wiemann{at}uni-essen.de Rationale: In vivo inhibition of the sodium/proton exchanger 3 (NHE3) in chemosensitive neurons of the ventrolateral brainstem augments central respiratory drive in anesthetized rabbits. Objectives: 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. Measurements and Main 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 PaCO2 (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 PaCO2 in conscious rabbits by adjusting the set point and the loop gain of the system.
Key Words: alveolar ventilation • arterial PCO2 • central chemosensitivity • metabolic rate • renal acid-base control This article has been cited by other articles:
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