Published ahead of print on June 9, 2005, doi:10.1164/rccm.200411-1567OC Am. J. Respir. Crit. Care Med., Volume 172, Number 2, July 2005, 244-249 A more recent version of this article appeared on July 15, 2005
Submitted on November 22, 2004 Sodium/Proton Exchanger 3 in the Medulla oblongata and Set Point of Breathing ControlMartin Wiemann1*,1 Department of Physiology, University of Duisburg-Essen, Essen, Germany, 2 Department of Physiology, Ruhr-University, Bochum, Germany * To whom correspondence should be addressed. E-mail: martin.wiemann{at}uni-essen.de.
Rationale: In vivo inhibition of the sodium/proton exchanger 3 (NHE3) in chemosensitive neurones of the ventrolateral brainstem augments central respiratory drive in anaesthetised rabbits. Objectives: To further explore the possible role of this exchanger for the control of breathing, we asked for 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, along with arterial and urinary acidbase status and renal base control. Expression of NHE3 in brainstem tissue from the obex region was determined by quantitative real-time RT-PCR analysis. Measurements and Main Results: With respect to 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/µg RNA, respectively. Alveolar ventilation of high brainstem NHE3 animals was lower than that of low NHE3 animals (715±36 vs. 919±41 mlmin-1; P<0.01), a finding also reflected by a marked difference in arterial PCO2 (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 re-absorption were not found to be different. Conclusion: We conclude that the level of brainstem NHE3 expression - most likely via intracellular pH modulation - contributes to the individual control of breathing and PCO2 in conscious rabbits by adjusting the set point and the loop gain of the system. Key words: alveolar ventilation, arterial PCO2, metabolic rate, central chemosensitivity, renal acid-base control
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