The effects of 3,4-diaminopyridine on acetylcholine release at the frog neuromuscular junction

The effects of 3,4-diaminopyridine (3,4-DAP) were studied on spontaneous and evoked transmitter release in the frog sartorius muscle preparation. At a concentration of 1 mM, 3,4-DAP caused the appearance of spontaneous giant potentials, this effect of 3,4-DAP also occurred in absence of extracellular calcium. At lower concentrations in magnesium Ringer 3,4-DAP (1-10 microM) increased e.p.p. quantal content without causing the appearance of spontaneous giant potentials, 3,4-DAP prolonged muscle action potential (1 mM) and it is suggested that prolongation of the nerve terminal action potential by 3,4-DAP contributes largely to the increased evoked acetylcholine release. The ability of 3,4-DAP to cause the appearance of giant spontaneous potentials is considered to be independent of the drug's known ability to inhibit potassium conductance in excitable membranes, and may be due to the release of performed multiquantal packets of acetylcholine as suggested for vinblastine. It is concluded that 3,4-DAP is a useful tool in the study of both evoked and spontaneous acetylcholine release.