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Departments of 1 Physiology I and 2 Internal Medicine, University of Tübingen, 72076 Tübingen, Germany
L-Carnitine is essential for the translocation of
acyl-carnitine into the mitochondria for 
-oxidation of long-chain
fatty acids. It is taken up into the cells by the recently cloned
Na+-driven carnitine organic cation transporter OCTN2. Here
we expressed hOCTN2 in Xenopus laevis oocytes and
investigated with two-electrode voltage- clamp and flux measurements
its functional and pharmacological properties as a
Na+-carnitine cotransporter. L-carnitine
transport was electrogenic. The L-carnitine-induced
currents were voltage and Na+ dependent, with half-maximal
currents at 0.3 ± 0.1 mM Na+ at 
60 mV. Furthermore,
L-carnitine-induced currents were pH dependent, decreasing
with acidification. In contrast to other members of the organic cation
transporter family, hOCTN2 functions as a Na+-coupled
carnitine transporter. Carnitine transport was stereoselective, with an
apparent Michaelis-Menten constant (Km) of
4.8 ± 0.3 µM for L-carnitine and 98.3 ± 38.0 µM for D-carnitine. The substrate specificity of hOCTN2
differs from rOCT-1 and hOCT-2 as hOCTN2 showed only small currents
with classic OCT substrates such as choline or tetraethylammonium; by
contrast hOCTN2 mediated transport of betaine. hOCTN2 was inhibited by
several drugs known to induce secondary carnitine deficiency. Most
potent blockers were the antibiotic emetine and the ion channel
blockers quinidine and verapamil. The apparent IC50 for
emetine was 4.2 ± 1.2 µM. The anticonvulsant valproic acid did
not induce a significant inhibition of carnitine transport, pointing to
a different mode of action. In summary, hOCTN2 mediates electrogenic
Na+-dependent stereoselective high-affinity transport of
L-carnitine and Na+. hOCTN2 displays transport
properties distinct from other members of the OCT family and is
directly inhibited by several substances known to induce systemic
carnitine deficiency.
carnitine transport; human sodium-driven organic cation transporter 2; pharmacology; secondary carnitine deficiency
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