Am J Respir Crit Care Med
Department of Physiology, Ruhr-University, 44780 Bochum, Germany.
Published: September 2007
Rationale: The sodium/proton exchanger (NHE) 3 is expressed in brainstem areas with prevalence for central chemosensitivity. Selective NHE3 inhibitors can evoke CO(2) mimetic responses both in vitro and in vivo, demonstrating the functional significance of this pH-regulating protein. Moreover, levels of NHE3 expression are inversely correlated to interindividual differences of baseline ventilation in conscious rabbits.
Objectives: We explored the influence of chronic acid-base disturbances on mRNA levels of brainstem NHE3 in relation to breathing control.
Methods: Alveolar ventilation (Va), blood gases, systemic base excess (BE), and metabolic Vco(2) were determined in rabbits shortly after exposure to either CO(2)-enriched air for 3 days (n = 5) or to ammonium chloride with drinking water for 2 days (n = 6). Untreated animals served as controls (n = 24). NHE3 mRNA within the obex region was quantified by real-time reverse transcription-polymerase chain reaction.
Measurements And Main Results: After chronic hypercapnia, we found a compensatory rise of BE (mean +/- SEM) to 5.3 +/- 0.5 mmol x L(-1) with slightly elevated Pa(CO(2)). Brainstem NHE3 mRNA as well as Va were not significantly different from control levels. In the NH(4)Cl group, arterial pH was approximately 0.09 units lower than control, and BE decreased to -6.5 +/- 1.6 mmol x L(-1) with slightly decreased Pa(CO(2)), but considerably reduced Va (by approximately 25%; P < 0.05) and Vco(2). Concomitantly, brainstem NHE3 mRNA had increased from control level of 1.45 +/- 0.19 to 3.64 +/- 0.37 fg cDNA/mug RNA; P < 0.01.
Conclusions: Expression of brainstem NHE3 is up-regulated by chronic metabolic acidosis but not by prolonged hypercapnia. It is proposed that elevated brainstem NHE3 expression contributes to limit maladaptive hyperventilation during metabolic acidosis.
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http://dx.doi.org/10.1164/rccm.200703-347OC | DOI Listing |
Int J Legal Med
May 2024
Institute of Legal Medicine, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
Auton Neurosci
May 2017
Department of Physiology, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil. Electronic address:
Presympathetic neurons in the rostral ventrolateral medulla (RVLM) including the adrenergic cell groups play a major role in the modulation of several reflexes required for the control of sympathetic vasomotor tone and blood pressure (BP). Moreover, sympathetic vasomotor drive to the kidneys influence natriuresis and diuresis by inhibiting the cAMP/PKA pathway and redistributing the Na/H exchanger isoform 3 (NHE3) to the body of the microvilli in the proximal tubules. In this study we aimed to evaluate the effects of renal afferents stimulation on (1) the neurochemical phenotype of Fos expressing neurons in the medulla oblongata and (2) the level of abundance and phosphorylation of NHE3 in the renal cortex.
View Article and Find Full Text PDFChin Med J (Engl)
June 2014
Department of Respiratory and Critical Care Medicine, Peking University First Hospital, Beijing 100034, China.
Background: Recent studies showed the central Na+/H+ exchanger type 3 (NHE3) has a close relationship with ventilation control. The objective of the study is to investigate the role of NHE3 in sleep apnea in Sprague-Dawley (SD) rats.
Methods: A sleep study was performed on 20 male SD rats to analyze the correlation between the sleep apneic events and total NHE3 protein content and inactive NHE3(pS552) in the brainstem measured by Western blotting.
Neurosci Bull
February 2014
Department of Respiratory and Critical Care Medicine, Peking University First Hospital, Beijing, 100034, China.
Extracellular pH (pHe) and intracellular pH (pHi) are important factors for the excitability of chemosensitive central respiratory neurons that play an important role in respiration and obstructive sleep apnea. It has been proposed that inhibition of central Na(+)/H(+) exchanger 3 (NHE-3), a key pHi regulator in the brainstem, decreases the pHi, leading to membrane depolarization for the maintenance of respiration. However, how intracellular pH affects the neuronal excitability of respiratory neurons remains largely unknown.
View Article and Find Full Text PDFJ Pediatr
January 2010
Institute of Forensic Medicine, University Hospital Essen, Essen, Germany.
Objective: To determine the contribution of variations in the sodium/proton exchanger 3 (NHE3) gene in sudden infant death syndrome (SIDS).
Study Design: Variations in the exons and promoter of the NHE3 gene were analyzed with direct sequencing analysis and mini sequencing (SNaPshot analysis) in 251 cases of SIDS, plus 50 infant control subjects who had died of other causes, and 170 healthy adults.
Results: The C2405T variant (exon 16) and 2 polymorphisms in the promoter (G1131A and C1197T) were encountered significantly more frequently in cases of SIDS than in control subjects.
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