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

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.