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Neuroscience. 1997 Jul;79(2):591-603.

Expression and localization of Na+/H+ exchangers in rat central nervous system.

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  • 1Department of Pediatrics, Yale University School of Medicine, New Haven, CT 06520, U.S.A.


Neurons in the central nervous system regulate their intracellular pH using particular membrane proteins of which two, namely the Na+-dependent Cl-/HCO3- exchanger and the Na+/H+ exchanger, are essential. In this study we examined messenger RNA expression and distribution of Na+/H+ exchanger in the newborn rat central nervous system and with maturation using Northern blot analysis and in situ hybridization. Our study clearly shows that each Na+/H+ exchanger has a different expression pattern in the rat central nervous system. As in non-excitable tissues, Na+/H+ exchanger 1 is by far the most abundant of all Na+/H+ exchangers in the rat central nervous system. Its expression is ubiquitous although its messenger RNA appears at higher levels in the hippocampus, in the 2nd/3rd layers of periamygdaloid cortex and in the cerebellum. The low level of messenger RNAs encoding Na+/H+ exchanger 2 and 4 is mainly expressed in the cerebral cortex and in the brainstem-diencephalon, while Na+/H+ exchanger 3 transcripts are found only in the cerebellar Purkinje cells. From a developmental point of view, Na+/H+ exchanger 1, 2 and 4 showed an increased level in their transcripts in the cerebral cortex while an opposite trend existed in the cerebellum from postnatal day 0 to postnatal day 30. The messenger RNA for Na+/H+ exchanger 3, however, increased its level with age in cerebellum. From our data we conclude that: i) the expression of the Na+/H+ exchanger is age-, region-, and subtype-specific, with Na+/H+ exchanger 1 being the most prevalent in the rat central nervous system; ii) specialization of groups of neurons with respect to the type of Na+/H+ exchanger is clearly illustrated by Na+/H+ exchanger 3 which is almost totally localized in cerebellar Purkinje cells; and iii) the developmental increase in the messenger RNA for Na+/H+ exchanger 1 in the cerebral cortex and hippocampus is consistent with our previous studies on intracellular pH physiology in neonatal and mature neurons. Together this study indicates that expression of each Na+/H+ exchanger messenger RNA is differentially regulated both during development and in the different regions of rat central nervous system.

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