The “Desensitizing” Effect of Acetylcholine on the Mammalian Motor End‐Plate.

Summary. A micro‐application technique has been used to study the desensitization which acetylcholine produces at the mammalian motor end‐plate. Acetylcholine was released by ionophoresis from a twin pipette near sensitive spots in the end‐plate region of a single muscle fibre, and the resulting potential changes were recorded by an intracellular electrode. Isolated muscles mounted in a constant temperature bath from the following mammalian species were used: guinea‐pig, rat, rabbit and cat. In all the investigated muscles a steady release of acetylcholine produced a loss of sensitivity in the end‐plate membrane. The degree and the speed of onset of desensitization was graded and increased with the applied concentration of acetylcholine while the rate of recovery was relatively constant. Marked species variations were observed in the intensity and time course of desensitization. In the guinea‐pig and the rabbit it was necessary to have a steady efflux of acetylcholine producing an initial depolarization of a few millivolts during several seconds to obtain desensitization. In the rat and the cat the same effect was generally achieved within a few tenths of a second by concentrations of acetylcholine producing less depolarization. The half‐times of recovery varied in a similar way. In the tenuissimus muscle of the cat a conditioning pulse of 10–20 msec duration causing only a few millivolts depolarization frequently produced an almost immediate desensitization lasting for more than one second. No desensitization was observed after single conditioning pulses of 1–2 msec duration but when several such pulses n‐ere given at a frequency of 3–6/sec considerable desensitization developed. It is suggested that the concentrations of acetylcholine which produce desensitization are, at least in certain mammalian muscles, within the range of concentrations normally produced at the end‐plate by a motor nerve impulse, and that consequently desensitization may develop during repetitive motor nerve stimulation.