Acute inhibitory effects of clenbuterol on force, Ca 2+ transients and action potentials in rat soleus may not involve the β 2-adrenoceptor pathway

1. Clenbuterol, a β 2-adrenoceptor agonist, can have inhibitory and myotoxic effects on slow-twitch muscles. Clenbuterol is lipophilic and may enter into the intracellular compartment, and because of this, it is likely that clenbuterol will have different effects to classical β 2-adrenoceptor agonists such as terbutaline. The aim of the present study is to investigate clenbuterol's effect on force, intracellular [Ca 2+] and electrophysiology, and the role of the β 2-adrenoceptor pathway in these effects. 2. Simultaneous measurements of isometric force and [Ca 2+] i were made from small bundles of rat soleus muscle fibres in which several superficial fibres had been pressure-injected with the fluorescence Ca 2+ indicator Indo-1. The muscle's electrophysiological response was measured using glass intracellular microelectrodes. 3. The most robust effect of clenbuterol was a concentration- (10-50μmol/L) and frequency-dependent (10-80Hz) loss of force and [Ca 2+] i maintenance during tetanic stimulation of muscle fibres. None of these effects were reduced in the presence of the β 2-antagonist ICI 118551. 4. In addition clenbuterol had a significant effect on muscle electrophysiology, with action potentials measured during tetanic trains being inhibited in a concentration- and frequency-dependent manner. This response was also unchanged by pre-treatment with the β 2-antagonist ICI 118551. 5. These results indicate that some of clenbuterol's effects are mediated through a pathway other than the β 2-adrenoceptors.