The expression of the Na+/Ca2+ exchanger was studied in differentiating mus
cle fibers in rats. NCX1 and NCX3 isoform (Na+/Ca2+ exchanger isoform) expr
ession was found to be developmentally regulated. NCX1 mRNA and protein lev
els peaked shortly after birth. Conversely, NCX3 isoform expression was ver
y low in muscles of newborn rats but increased dramatically during the firs
t 2 wk of postnatal life. Immunocytochemical analysis showed that NCX1 was
uniformly distributed along the sarcolemmal membrane of undifferentiated ra
t muscle fibers but formed clusters in T-tubular membranes and sarcolemma o
f adult muscle. NCX3 appeared to be more uniformly distributed along the sa
rcolemma and inside myoplasm. In the adult, NCX1 was predominantly expresse
d in oxidative (type 1 and 2A) fibers of both slow- and fast-twitch muscles
, whereas NCX3 was highly expressed in fast glycolytic (2B) fibers. NCX2 wa
s expressed in rat brain but not in skeletal muscle. Developmental changes
in NCX1 and NCX3 as well as the distribution of these isoforms at the cellu
lar level and in different fiber types suggest that they may have different
physiological roles.