Proceedings of The Physiological Society
University of Manchester (2010) Proc Physiol Soc 19, C63
The effects of clenbuterol on force in isolated intact mouse skeletal muscle fibre bundles are not mediated through ??2-adrenoceptor
G. Mutungi1, L. Alexandre1
1. Biomedical and Clinical Sciences Research Institute, University of East Anglia, Norwich, United Kingdom.
In a previous communication we showed that clenbuterol, a long-acting β2-adrenoceptor agonist, decreases force production in mouse fast- and slow-twitch skeletal muscle fibre bundles (Treen and Mutungi, 2009). However, the mechanism underlying this effect is still poorly understood. Therefore, the primary aim of this study was to investigate the mechanism underlying the acute actions of clenbuterol in mouse skeletal muscle fibre bundles. All the experiments were performed at 20 ± 0.1°C on small muscle fibre bundles isolated from the edl and soleus muscles of adult mice. The mice were humanely killed and all the experiments conformed to the Animals (Scientific Procedures) Act 1986. The fibre bundles were perfused with the standard Ringer’s solution (controls) or the standard Ringer’s solution plus 50µM clenbuterol. Twitch and tetanus were continuously monitored and pharmacological interventions were used to investigate the mechanism underlying the actions of clenbuterol. Treating the muscle fibre bundles with clenbuterol led to a 56 ± 3% (n=8) and 54 ± 5% (n=6) decrease in maximum isometric tension in the fast- and slow-twitch fibres, respectively. The drop in force occurred within 15 minutes after the application of clenbuterol and was completely reversible. However, it was insensitive to propranolol (a general β-blocker), ICI118551 (a β2 specific blocker) and the protein kinase A (PKA) inhibitor, 14-22 amide. These results show that the effects of clenbuterol on force production in isolated mouse fast- and slow-twitch muscle fibre bundles are not mediated through the β2-adrenoceptor and PKA. From these findings we suggest that clenbuterol may act directly to inhibit cross-bridge cycling.
Where applicable, experiments conform with Society ethical requirements