Acute inhibitory effects of clenbuterol on force, Ca²⁺ transients and action potentials in rat soleus may not involve the β₂-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+) 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- (10-50 μmol/L) and frequency-dependent (10-80 Hz) loss of force and Ca(2+) 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.