Desensitization, as represented by the progressive decline in the electromotive effects of depolarizing agents at the neuromuscular junction, was studied by observing the time course of changes in effective transmembrane resistance during the prolonged application of 0.27 mM carbamylcholine to the postjunctional region of frog skeletal muscle fibers. The effective transmembrane resistance was measured by means of two intracellular microelectrodes implanted in the junctional region of single muscle fibers. When carbamylcholine was applied to the muscle there was an immediate decrease in the effective membrane resistance followed by a slower return toward control values which was identified as the phase of desensitization. When the calcium concentration was increased from 0 to 10 mM there was an approximately sevenfold increase in the rate of desensitization. On the other hand, an increase in the concentration of sodium from 28 to 120 mM caused a slowing of the rate of desensitization. Even in muscles depolarized by potassium sulfate, calcium increased the rate of desensitization while high concentrations of potassium tended to prolong the process. Some mechanisms by which calcium might exert these effects are discussed.

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