Contractile performance of isolated muscle from mice over-expressing uncoupling protein 3

King's College London (2005) J Physiol 565P, C97

Communications: Contractile performance of isolated muscle from mice over-expressing uncoupling protein 3

Bickham, Dale Colin; Curtin, Nancy ;

1. Biological Structure and Function Section, Division of Biomedical Sciences, Imperial College London, London, United Kingdom.

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Uncoupling protein 3 (UCP3) is a mitochondrial transporter, which is specific to skeletal muscle, and allows protons to proceed through the membrane without synthesis of ATP. Transgenic mice over-expressing UCP3 (UCP3-oe) are lean despite being hyperphagic and having a normal level of locomotion (Clapham et al. 2000). Experiments on isolated muscle have shown the recovery heat production after isometric contraction is higher when extra UCP3 is present (Curtin et al. 2002), indicating inefficient production of ATP. Muscle fibre types are characterized by their myosin isoform content and metabolic profile. For example, the type-1 fibres common in mouse soleus contain a slow myosin isoform and have a high capacity for mitochondrial/oxidative production of ATP. Disruption of the matching of contractile proteins and metabolism may result in altered contractile performance. We report here the performance of fully rested soleus (sol) and extensor digitorum longus (edl) muscles from wild-type (wt) and UCP3-oe during contraction whilst shortening. All experiments were done on muscles isolated from mice that had been killed humanely. Soleus muscles were tetanized at 75 Hz and edl at 125 Hz (25°C). The ‘step and ramp’ method was used to measure the force-velocity relationship of the contractile elements (Curtin et al. 1998); muscles were stimulated isometrically for 0.2 s before shortening. The slack test method (Edman, 1977) was also used to measure the velocity of shortening under zero load. Muscles from wt and UCP3-oe mice had similar Vmax values, maximum velocities of shortening (mean± s.e.; wt sol, 5.08 ± 0.23, n=11; UCP3-oe sol, 4.98 ± 0.61, n=7; wt edl, 7.84 ± 0.31, n=8; UCP3-oe edl, 8.39 ± 0.60, n=7: units Lo/s where Lo is fibre length giving maximum isometric force, Po) and similar maximum power outputs (wt sol, 0.081 ± 0.006, n=11; UCP3-oe sol, 0.074 ± 0.007, n=7; wt edl, 0.100 ± 0.002, n=8; UCP3-oe edl, 0.109 ± 0.006, n=7: units /PoVmax). We conclude that over-expression of UCP3 does not affect these aspects of the contractile performance.



Where applicable, experiments conform with Society ethical requirements.

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