Muscle contraction increases carnitine uptake via translocation of OCTN2.
Since carnitine plays an important role in fat oxidation, influx of carnitine could be crucial for muscle metabolism. OCTN2 (SLC22A5), a sodium-dependent solute carrier, is assumed to transport carnitine into skeletal muscle cells. Acute regulation of OCTN2 activity in rat hindlimb muscles was investigated in response to electrically induced contractile activity. The tissue uptake clearance (CL(uptake)) of l-[(3)H]carnitine during muscle contraction was examined in vivo using integration plot analysis. The CL(uptake) of [(14)C]iodoantipyrine (IAP) was also determined as an index of tissue blood flow. To test the hypothesis that increased carnitine uptake involves the translocation of OCTN2, contraction-induced alteration in the subcellular localization of OCTN2 was examined. The CL(uptake) of l-[(3)H]carnitine in the contracting muscles increased 1.4-1.7-fold as compared to that in the contralateral resting muscles (p<0.05). The CL(uptake) of [(14)C]IAP was much higher than that of l-[(3)H]carnitine, but no association between the increase in carnitine uptake and blood flow was obtained. Co-immunostaining of OCTN2 and dystrophin (a muscle plasma membrane marker) showed an increase in OCTN2 signal in the plasma membrane after muscle contraction. Western blotting showed that the level of sarcolemmal OCTN2 was greater in contracting muscles than in resting muscles (p<0.05). The present study showed that muscle contraction facilitated carnitine uptake in skeletal muscles, possibly via the contraction-induced translocation of its specific transporter OCTN2 to the plasma membrane.
Graduate School of Natural Science and Technology, Kanazawa University, Kanazawa, Japan.
Yasuro
Y
Furuichi
Tomoko
T
Sugiura
Yukio
Y
Kato
Hisashi
H
Takakura
Yoshiteru
Y
Hanai
Takeshi
T
Hashimoto
Kazumi
K
Masuda
D000818:Animals; D001692:Biological Transport; D002331:Carnitine / Q000378:metabolism*; D008297:Male; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000378:metabolism*; D027701:Organic Cation Transport Proteins / Q000378:metabolism*; D021381:Protein Transport; D051381:Rats; D017208:Rats, Wistar; D000074058:Solute Carrier Family 22 Member 5
D027701:Organic Cation Transport Proteins; C115441:Slc22a5 protein, rat; D000074058:Solute Carrier Family 22 Member 5; D002331:Carnitine