4-Aminopyridine does not increase m.e.p.p. frequencies at junctions depolarized by potassium.

4-aminopyridine (4-AP) is known to produce large increases in quantal acetylcholine release from stimulated motor nerve terminals. It has been suggested that the drug might act directly on Ca2+ channels to increase Ca2+ influx. This possibility was tested at frog neuromuscular junctions depolarized in elevated [K+]out. The 4-AP did not increase miniature end-plate potential frequencies. Also, 4-AP did not alter the increase in frequency that follows a rise in [Ca2+]out at a depolarized junction. Therefore, under these conditions, 4-AP does not appear to change Ca2+ entry into or elimination from the nerve terminal. The results support the hypothesis that 4-AP acts by lengthening the nerve terminal action potential.