Am. Pajor et al., SODIUM AND LITHIUM INTERACTIONS WITH THE NA+ DICARBOXYLATE COTRANSPORTER/, The Journal of biological chemistry, 273(30), 1998, pp. 18923-18929
The two-electrode voltage clamp was used to study the currents associa
ted with transport of succinate by the cloned Na+/dicarboxylate cotran
sporter, NaDC-1, expressed in Xenopus oocytes, The presence of succina
te induced inward currents which were dependent on the concentrations
of succinate and sodium,;md on the membrane potential. At -50 mV, the
K-0.5(succinate) was 180 mu M and the K-0.5(Na+) was 19 mM. The Hill c
oefficient was 2.3, which is consistent with a transport stoichiometry
of 3 Na+:1 divalent anion substrate. Currents wt:re induced in NaDC-1
by a range of di- and tricarboxylates, including citrate, methylsucci
nate, fumarate, and tricarbally-late. Although Na+ is the preferred ca
tion, Li+ was also able to support transport. The K-0.5(succinate) was
approximately 10-fold higher in Li+ compared with Na+. In the presenc
e of Na+, however, Li+ was a potent inhibitor of transport. Millimolar
concentrations of Li+ resulted in decreases in apparent succinate aff
inity and in the I-max(succinate). Furthermore, lithium inhibition und
er saturating sodium concentrations showed hyperbolic kinetics, sugges
ting that one of the three cation binding sites in NaDC-1 has a higher
affinity for Li+ than Na+. We conclude that NaDC-1 is an electrogenic
anion transporter that accepts either Na+ or Li+ as coupling cations.
However, NaDC-1 contains a single high affinity binding site for Lithat, when occupied,. results in transport inhibition, which may accou
nt for its potent inhibitory effects on renal dicarboxylate transport.