A comparison of the effect of cholinesterase inhibitors on end-plate current and on cholinesterase activity in frog muscle

The effect of various cholinesterase inhibitors on the end-plate current was studied in glycerol-treated frog skeletal muscle. In the same muscle, the activity of cholinesterases was estimated histochemically and measured quantitatively.By using the irreversibile cholinesterase inhibitor methanesulphonyl fluoride, cholinesterases were completely inhibited. This resulted in an increase of the amplitude, of the rise time and half-time of the end-plate current.By using the reversible cholinesterase inhibitors eserine and prostigmine, the changes of the end-plate current seemed complex and not well understood. At concentrations of these drugs which did not inhibit the activity of cholinesterases completely, the amplitude, the rise time and the half-time of the end-plate current were increased by a variable extent. At a higher concentration, which almost completely inhibited the cholinesterases, the amplitude and the half-time of the end-plate current were depressed. This was particularly well pronounced with the cholinesterase inhibitor BW284C51.The changes in the end-plate current, observed at a relatively high concentration of reversible inhibitors, are thought to be related either to a presynaptic, or to a postsynaptic “curare-like” action of these drugs.