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Blockade of Na+/H+ exchanger type 3 causes intracellular acidification and hyperexcitability via inhibition of pH-sensitive K+ channels in chemosensitive respiratory neurons of the dorsal vagal nucleus in rats.
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 PDFpH regulating transporters in neurons from various chemosensitive brainstem regions in neonatal rats.
Am J Physiol Regul Integr Comp Physiol
November 2009
Department of Neuroscience, Cell Biology and Physiology, Wright State University Boonshoft School of Medicine, Dayton, Ohio 45435, USA.
We studied the membrane transporters that mediate intracellular pH (pH(i)) recovery from acidification in brainstem neurons from chemosensitive regions of neonatal rats. Individual neurons within brainstem slices from the retrotrapezoid nucleus (RTN), the nucleus tractus solitarii (NTS), and the locus coeruleus (LC) were studied using a pH-sensitive fluorescent dye and fluorescence imaging microscopy. The rate of pH(i) recovery from an NH(4)Cl-induced acidification was measured, and the effects of inhibitors of various pH-regulating transporters determined.
View Article and Find Full Text PDFRole of brainstem sodium/proton exchanger 3 for breathing control during chronic acid base imbalance.
Am J Respir Crit Care Med
September 2007
Department of Physiology, Ruhr-University, 44780 Bochum, Germany.
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.
View Article and Find Full Text PDFBrainstem NHE-3 expression and control of breathing.
Adv Exp Med Biol
March 2005
Department of Physiology, University of Essen, Essen, Germany.
Chronic metabolic acidosis enhances NHE-3 protein abundance and transport activity in the rat thick ascending limb by increasing NHE-3 mRNA.
J Clin Invest
January 1997
Institut National de la Santé et de la Recherche Médicale U.356, Université Pierre et Marie Curie, Centre Hospitalo-Universitaire Broussais, Paris, France.
Chronic metabolic acidosis (CMA) is associated with an adaptive increase in the bicarbonate absorptive capacity of the rat medullary thick ascending limb (MTAL). To specify whether NHE-3, the apical MTAL Na/H exchanger, is involved in this adaptation, NHE-3 mRNA was quantified by a competitive RT-PCR using an internal standard which differed from the wild-type NHE-3 mRNA by an 80-bp deletion. CMA increased NHE-3 mRNA from 0.
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