Influence of muscle activity on the actions of chloride channel blockers in the mouse skeletal muscle.

The purpose of this work was to investigate the effect of channel blockers in the presence and absence of nerve and/or muscle activity. 9-Anthracenecarboxylic acid (0.03 mM), a chloride channel blocker, increased both the amplitude and duration of the contractile response to direct stimulation in the mouse soleus muscle in either low Ca2+ Krebs (0.25 mM) or normal Ca2+ Krebs (2.5 mM) containing 0.1 mM 4-aminopyridine (potassium channel blocker). In addition, spontaneous contractions were induced by 9-anthracenecarboxylic acid in low Ca2+ Krebs. On the other hand, the combination of two potassium channel blockers, 4-aminopyridine (0.3 mM) plus tetraethylammonium ion (10 mM), increased the twitch amplitude but only slightly increased the contractile duration in the mouse soleus muscle in normal Krebs. The contraction-potentiating actions of 9-anthracenecarboxylic acid were inhibited by denervation, while those of 4-aminopyridine plus tetraethylammonium were not. Chronic exposure to the sciatic nerve to a lidocaine-cuff, but not to a colchicine-cuff, exhibited similar effects as denervation. Direct electrical stimulations were applied for 2 days to the soleus muscle through implanted teflon-coated multistranded electrodes in vivo, beginning immediately after denervation or cuff treatments. The contraction-potentiating effects of 4-aminopyridine plus 9-anthracenecarboxylic acid or 9-anthracenecarboxylic acid in low Ca2+ Krebs were restored in the denervated or lidocaine-cuff-treated soleus muscle by chronic direct stimulations. The membrane potential and input resistance of muscle fibres and the effects of 9-anthracenecarboxylic acid, which were altered by denervation or cuff treatment, were also partially restored by this measure. When sciatic nerves had been treated with lidocaine-cuff for 4 days and the cuff was then removed for 7 days, the contraction-potentiating effects of 9-anthracenecarboxylic acid were also restored. Four days after Achilles tenotomy, the contraction-potentiating effects of 9-anthracenecarboxylic acid were markedly inhibited. It was concluded that muscle activity controls the properties of chloride channels and that neural activity may affect the properties of chloride channels via enhancement of the muscle contraction.