Effect of 4-aminopyridine on nerve terminal action potentials.

The effects of 4-aminopyridine (4AP) on the extracellularly recorded nerve terminal action potential (NTAP) and end-plate potential were studied at the frog neuromuscular junction. An in-depth analysis of the time course of the NTAP was performed in the presence and absence of extracellular Ca++. Low concentrations (5 X 10(-6) M) of 4AP produced no significant alterations in the time course of the NTAP, yet increased quantal content of the end-plate potential 2-fold. In contrast, high concentrations (5 X 10(-4) M) of 4AP prolonged the duration of the NTAP by selectively flattening the K+ slope of the NTAP and increased the quantal content of the end-plate potential. It is concluded that both potassium channel blockade and facilitation of transmitter release by 4AP can be demonstrated in this preparation, and that it is possible to separate these actions by varying the concentration of 4AP. Interpretation of these data suggests that there is a second site or mechanism of action by which 4AP potentials transmitter release. Possible mechanisms of action for 4AP are discussed.