Chronic low-frequency stimulation upregulates uncoupling protein-3 in transforming rat fast-twitch skeletal muscle

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology Vol. 287; no. 6; p. R1419
• Main Authors: Putman, Charles T, Dixon, Walter T, Pearcey, Jean A, Maclean, Ian M, Jendral, Michelle J, Kiricsi, Mónika, Murdoch, Gordon K, Pette, Dirk
• Format: Journal Article
• Language: English
• Published: United States 01-12-2004
• Subjects: 3-Hydroxyacyl CoA Dehydrogenases - genetics; Actins - genetics; Animals; Carrier Proteins - genetics; Carrier Proteins - metabolism; Electric Stimulation; Gene Expression Regulation; Kinetics; Male; Membrane Transport Proteins; Mitochondria, Muscle - physiology; Mitochondrial Membrane Transport Proteins; Mitochondrial Proteins; Mitochondrial Uncoupling Proteins; Muscle Fibers, Fast-Twitch - physiology; Muscle, Skeletal - physiology; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Rats; Rats, Wistar; RNA, Messenger - genetics; Time Factors
• ISSN: 0363-6119
• DOI: 10.1152/ajpregu.00421.2004

The purpose of this investigation was to examine the temporal changes in uncoupling protein (UCP)-3 expression, as well as related adaptive changes in mitochondrial density and fast-to-slow fiber type transitions during chronically enhanced contractile activity. We examined the effects of 1-42 days of chronic low-frequency electrical stimulation (CLFS), applied to rat tibialis anterior (TA) for 10 h/day, on the expression of UCP-3 and concomitant changes in myosin heavy chain (MHC) protein expression and increases in oxidative capacity. UCP-3 protein content increased from 1 to 12 days, reaching 1.5-fold over control (P < 0.0005); it remained elevated for up to 42 days. In contrast, UCP-3 mRNA decreased in response to CLFS, reaching a level that was threefold lower than control (P < 0.0007). The activities of the mitochondrial reference enzymes citrate synthase (EC 4.1.3.7) and 3-hydroxyacyl-CoA-dehydrogenase (EC 1.1.1.35), which are known to increase in proportion to mitochondrial density, progressively increased up to an average of 2.3-fold (P < 0.00001). These changes were accompanied by fast-to-slow fiber type transitions, characterized by a shift in the pattern of MHC expression (P <0.0002): MHCI and MHCIIa expression increased by 1.7- and 4-fold, whereas MHCIIb displayed a 2.4-fold reduction. We conclude that absolute increases in UCP-3 protein content in the early adaptive phase were associated with the genesis of mitochondria containing a normal complement of UCP-3. However, during exposure to long-term CLFS, mitochondria were generated with a lower complement of UCP-3 and coincided with the emergence of a growing population of oxidative type IIA fibers.