Effect of denervation on a steady electric current generated at the end-plate region of rat skeletal muscle.

An electric current flows continuously out of the synaptic region of rat lumbrical muscle fibres. It is generated apparently as a result of a non-uniform Cl- conductance (GCl), with GCl being lowest at the end-plate. We investigated the effects of denervation on this current. The current persisted with little change after denervation. This was somewhat unexpected, since GCl falls dramatically after denervation, and in acute experiments on normal muscles, the steady current is greatly reduced by agents which block GCl. The steady current was blocked in denervated muscle, as in normal muscle, by low-Cl- solutions, Na+-free and K+-free solutions, and treatment with furosemide and 9-anthracene-carboxylic acid. The current in denervated muscle appears to be generated by the same general mechanism as in normal muscle. The results suggest that the [Cl-]i is significantly higher in denervated than in normal muscle fibres. Preliminary experiments with Cl- -selective micro-electrodes have confirmed this: [Cl-]i rises from about 12 mM to about 23 mM after denervation. This has the effect of moving the Cl- equilibrium potential (ECl) in a positive direction, so that the driving force for passive Cl- efflux is increased. The increased driving force compensates for the reduced GCl, allowing the steady current to persist in denervated fibres.