Effect of 4-aminopyridine on end-plate receptor desensitization caused by carbachol

The effect of 4-aminopyridine on receptor desensitization was investigated in the isolated rat diaphragm by measuring transmembrane potential in the end-plate region. When 4-aminopyridine was added to the bath before carbachol, the depolarization produced by the agonist was permanent, that is 4-aminopyridine completely inhibited the receptor desensitization produced by prolonged exposure of the receptors to carbachol. When it was added after carbachol in the phase in which the membrane had already repolarized, the end-plate region depolarized. Therefore, 4-aminopyridine was also able to reverse the receptors from the desensitized state to the resting non-desensitized one. The effect of 4-aminopyridine was concentration-dependent. Calcium antagonized the effect of 4-aminopyridine. 4-Aminopyridine also reversed the receptors from their desensitized state to the resting one in the isolated and chronically denervated rat hemidiaphragm. The known action of the aminopyridines cannot explain the effect of 4-aminopyridine described here. It is suggested that it is caused by an action on either the receptor-ionic channel complex or the lipids of the postjunctional membrane surrounding it.