Expression Of Novel Organic Cation/carnitine Transporter (octn2) In The Skeletal Muscle

Abstract

The primary function of L-carnitine is to facilitate the transport and the metabolism of long-chain fatty acids into the mitochondria for beta-oxidation and energy production. Since L-carnitine is unable to be synthesized in skeletal muscle, this molecule has to be influx from the blood. However, the mechanism of trans-sarcolemmal L-carnitine transport system remains unclear. Novel organic cation transporter 2 (OCTN2), a sodium-dependent solute carrier, transports L-carnitine from the plasma into cells and is expressed in tissues such as kidney, liver and intestine. Although OCTN2 is also assumed to transport L-carnitine across plasma membrane in skeletal muscle cell, there has been no report to detect the expression of OCTN2 in skeletal muscles. PURPOSE: The purpose of the present study was to show the expression of OCTN2 in various skeletal muscles. Additionally, we compared the OCTN2 expressions between metabolically heterogeneous rat hindlimb muscles in order to establish relationship between the amount of OCTN2 and capacity of muscle fatty acid oxidation. METHODS: Experiments were performed on male Wistar rats (12-wk old). Hindlimb muscles (m. soleus, m. plantaris, red and white portions of m. gastrocnemius), hearts and kidneys were homogenized in RIPA buffer and centrifuged to remove nuclear fractions and debris. The supernatant was used for analysis of Western blotting, and the expression of OCTN2 was investigated. RESULTS: OCTN2 was detected in heart and in red muscles (m. soleus and red portion of m. gatrocnemius), but not detected in m. plantaris and white portion of m. gastrocnemius. Expression of OCTN2 in kidney was more than ten times higher than heart and red skeletal muscles. The difference of expression level of OCTN2 gene product among kidney and other tissues agree to that for rat OCTN2 mRNA observed in the previous studies. CONCLUSIONS: In spite of small amount relative to kidney, OCTN2 was detectable in skeletal muscles especially slow-twitch red muscles, indicating that OCTN2 might contribute to fatty acid oxidation in skeletal muscles. These results suggest that OCTN2 transports L-carnitine from plasma into muscle cells, especially more in highly oxidative muscles.