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Sodium and lithium interactions with the Na+/Dicarboxylate cotransporter
A M Pajor1, B A Hirayama, D D Loo
1Department of Physiology, University of Arizona, Tucson, Arizona 85724, USA. Pajor@biosci.arizona
The Journal of Biological Chemistry
|July 21, 1998
Summary
The cloned Na+/dicarboxylate cotransporter (NaDC-1) facilitates succinate transport using sodium ions. Lithium can also support transport but acts as a potent inhibitor by binding to a high-affinity site.
Area of Science:
- Molecular biology
- Biochemistry
- Membrane transport
Background:
- The Na+/dicarboxylate cotransporter (NaDC-1) plays a crucial role in cellular dicarboxylate uptake.
- Understanding the ion dependency and substrate specificity of NaDC-1 is vital for comprehending renal dicarboxylate reabsorption.
Purpose of the Study:
- To investigate the transport mechanism and ion coupling of the cloned NaDC-1.
- To determine the stoichiometry and kinetics of succinate transport mediated by NaDC-1.
- To elucidate the role of sodium and lithium ions in NaDC-1 function.
Main Methods:
- Two-electrode voltage clamp electrophysiology in Xenopus oocytes expressing NaDC-1.
- Kinetic analysis of succinate and sodium concentration-dependent currents.
- Investigation of cation (Na+, Li+) effects on transport activity.
Main Results:
- NaDC-1 mediates electrogenic transport of succinate, dependent on succinate and sodium concentrations and membrane potential.
- Transport stoichiometry is suggested to be 3 Na+:1 divalent anion substrate.
- Lithium ions can support NaDC-1 transport but act as a potent inhibitor, indicating a high-affinity lithium binding site.
Conclusions:
- NaDC-1 is an electrogenic anion transporter utilizing either Na+ or Li+ as coupling cations.
- A high-affinity lithium binding site on NaDC-1 inhibits transport, potentially explaining lithium's effect on renal dicarboxylate transport.