B. Linck et al., FUNCTIONAL COMPARISON OF THE 3 ISOFORMS OF THE NA+ CA2+ EXCHANGER (NCX1, NCX2, NCX3)/, American journal of physiology. Cell physiology, 43(2), 1998, pp. 415-423
Three distinct mammalian Na+/Ca2+ exchangers have been cloned: NCX1, N
CX2, and NCX3. We have undertaken a detailed functional comparison of
these three exchangers. Each exchanger was stably expressed at high le
vels in the plasma membranes of BHK cells. Na+/Ca2+ exchange activity
was assessed using three different complementary techniques: Na+ gradi
ent-dependent Ca-45(2+) uptake into intact cells, Na+ gradient-depende
nt Ca-45(2+) uptake into membrane vesicles isolated from the transfect
ed cells, and exchange currents measured using giant patches of excise
d cell membrane. Apparent affinities for the transported ions Na+ and
Ca2+ were markedly similar for the three exchangers at both membrane s
urfaces. Likewise, generally similar responses to changes in pH, chymo
trypsin treatment, and application of various inhibitors were obtained
. Depletion of cellular ATP inhibited NCX1 and NCX2 but did not affect
the activity of NCX3. Exchange activities of NCX1 and NCX3 were modes
tly increased by agents that activate protein kinases A and C. All exc
hangers were regulated by intracellular Ca2+. NCX1-induced exchange cu
rrents were especially large in excised patches and, like the native m
yocardial exchanger, were stimulated by ATP. Results may be influenced
by our choice of expression system and specific splice variants, but,
overall, the three exchangers appear to have very similar properties.