Effects of terbutaline, a β2-adrenergic agonist, on the membrane potentials of innervated and denervated fast- and slow-twitch muscles

Abstract

Terbutaline (0.1 to 1000 μ m) produced a variable degree of hyperpolarization (2 to 3 mV) of innervated fibers on the surface of the fast-twitch extensor digitorum longus (extensor) and the slow-twitch soleus muscles from adult rats. Intracellular analysis of action potentials suggested that this effect of the β 2-agonist was associated with a decrease in the intracellular concentration of sodium [Na] i from 19.5 to 16.6 m m for the extensor and from 28.1 to 18.1 m m for the soleus. Terbutaline did not prevent ouabain (2 × 10 −4 m) from causing an approximately 10-mV decrease in the resting membrane potential (RMP) of these muscles. At 7 days after denervation, fibers of the extensor and soleus were depolarized an average of 21.1 and 13.7 mV, respectively. There was a corresponding increase in [Na] i to 27.5 and 34.8 m m. Also, ouabain failed to cause a further decrease in the RMP of the denervated extensor and that of the soleus was now depolarized by only 4 mV. Exposure of the muscles to terbutaline (10 μ m) partially reversed these effects of denervation. Specifically, the RMP was increased by 12.3 and 4.6 mV, respectively, for the extensor and soleus muscles. This was associated with the restoration of the ouabain-sensitive fraction of the RMP as well as a decrease in [Na] i to normal. The β-blocking drug propranolol completely prevented the effects of terbutaline on the RMP of the denervated muscles. The differences in the response of the extensor and soleus to terbutaline, as well as the effects of denervation on these responses, are discussed in terms of an adenylate cyclase pathway of muscle believed to mediate the effects of catecholamines on the RMP.