Facilitation by 3,4-diaminopyridine of regenerative acetylcholine release from mouse motor nerve.

1. Effects of 3,4-diaminopyridine (DAP) on endplate potentials (e.p.ps) were studied in mouse phrenic nerve-hemidiaphragms. 2. In cut muscle preparations, low concentrations of DAP (2-20 microns) increased the amplitude of e.p.ps and shifted the curve relating Ca2+ concentration to e.p.p. amplitude leftward. 3. High concentration of DAP (40-4000 microns) prolonged the duration of e.p.ps dose-dependently up to one hundred fold (ca. 200 ms), yielding, in addition to the normal phasic e.p.p., a prolonged plateau depolarization component which was often preceded by an upstroke depolarization. During the plateau depolarization, nerve stimulations did not evoke any e.p.p. 4. The plateau component of prolonged e.p.ps was suppressed by tubocurarine, verapamil, nifedipine, Mn2+ and Cd2+ (but not by atropine) at low concentrations that had negligible effect on the amplitude of miniature e.p.ps or the phasic component of e.p.ps. Abolition of the plateau component by these agents restored the capability of the nerve terminal to evoke e.p.ps on nerve stimulation. 5. Low concentrations of neostigmine (0.01-0.02 microns) markedly lengthened DAP-prolonged e.p.ps. However, the regenerative endplate depolarization evoked in the presence of high concentrations of neostigmine (0.3-0.5 microns) was not prolonged by DAP. 6. Tetraethylammonium (1 mM) did not provoke prolonged e.p.ps but acted cooperatively with DAP to prolong the duration of plateau depolarization. At a high concentration (3 mM), tetraethylammonium depressed the amplitude of miniature e.p.ps and abolished DAP-prolonged e.p.ps. 7. In uncut muscle preparations, DAP apparently did not modify the time course and amplitude of miniature e.p.ps.(ABSTRACT TRUNCATED AT 250 WORDS)