The antagonistic effects of calcium and potassium on the time course of action of carbamylcholine at the neuromuscular junction.

The electrogenic action of carbamylcholine on the postjunctional membrane of muscle fibers disappears gradually over a period of several seconds even when this agent is applied by constant perfusion. This waning of drug action, termed "desensitization" by some investigators, occurs also at other cholinergic synapses. It has been found in earlier studies that increased amounts of calcium in the extracellular medium can cause the desensitization process to occur more rapidly and that potassium tends to oppose this action of calcium. In the present investigation, it is found that the relative effects of these ions can be expressed in terms of the quantity (Ca)/(K)(1.7). A simple ion-exchange mechanism is proposed in which one calcium ion or two potassium ions are able to combine with an anionic site near the cell surface. A general relation between the time course of conductance changes and the extracellular concentration of the ions is derived which appears to be consistent with the conductance measurements over a period of 60 seconds and in the range of calcium concentrations from 0.05 to 20 millimoles/liter and of potassium from 33 to 165 millimoles/liter. Further experiments are presented which suggest that the time course of conductance changes under these conditions is limited primarily by the rate of increase of the calcium concentration at the exchange site.