Changes in the ionic currents sensitivity to inhibitors in twitch rat skeletal muscles following denervation

Under voltage clamp conditions, using the double mannitol gap technique, ionic currents developed by fast (e.d.l.) and slow (soleus) twitch muscle fibers of the rat were analysed at different times following denervation and the results compared with those obtained in normal cells. In slow fibers, denervation caused the appearance of a new population of TTX-resistant Na+ channels (dissociation constant K2 = 2,800 nM) compared with the normal TTX-sensitive Na+ channels (K1 = 9 nM). This new population of Na channels appeared in 5 days and contributed about 32% of the total Na conductance. Denervated fast fibres developed a slow component in the delayed outward current which was found to be typical of slow innervated muscles. This component appeared 5 to 20 days after nerve section. These changes are associated with modifications of potassium channels' sensitivity for specific inhibitors (TEA and 4-AP). After denervation, the delayed outward current in the two types of muscles becomes resistant to 4-AP whereas TEA, which blocks the total delayed outward current in innervated fibers (dissociation constant of 21.4 mM) becomes more effective in blocking the fast component (dissociation constant of 0.61 mM) and less effective in blocking the slow component in denervated cells. The analysis of the characteristics of the TEA sensitive and TEA insensitive components of the outward current leads to the proposal that these components were related to the fast and to the slow components previously described in fast and slow twitch mammalian skeletal muscles.