Acute inhibitory effects of clenbuterol on force, Ca2+ transients and action potentials in rat soleus may not involve the beta(2)-adrenoceptor pathway

作者：Head Stewart I^*; Ha Tuyen N V

来源：CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, 2011, 38(9): 638-646.

DOI：10.1111/j.1440-1681.2011.05574.x

• action potentials
• beta-adrenoceptors
• clenbuterol
• excitation-contraction coupling
• ICI 118551
• skeletal muscle
• terbutaline

1. Clenbuterol, a beta(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 beta(2)-adrenoceptor agonists such as terbutaline. The aim of the present study is to investigate clenbuterol's effect on force, intracellular [Ca2+] and electrophysiology, and the role of the beta(2)-adrenoceptor pathway in these effects.
2. Simultaneous measurements of isometric force and [Ca2+](i) were made from small bundles of rat soleus muscle fibres in which several superficial fibres had been pressure-injected with the fluorescence Ca2+ 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 mu mol/L) and frequency-dependent (10-80 Hz) loss of force and [Ca2+](i) maintenance during tetanic stimulation of muscle fibres. None of these effects were reduced in the presence of the beta(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 beta(2)-antagonist ICI 118551.
5. These results indicate that some of clenbuterol's effects are mediated through a pathway other than the beta(2)-adrenoceptors.

• 出版日期2011-9