4‐AMINOPYRIDINE AND EVOKED TRANSMITTER RELEASE FROM MOTOR NERVE ENDINGS

Abstract

1 In the presence of tetrodotoxin, electrotonic depolarization of frog motor nerve terminals causes the appearance of stimulus-graded endplate potentials. When 4-aminopyridine is added, the graded endplate potential is converted into a triggered all-or-none response resulting in giant endplate potentials of about 70 mV amplitude and 50 ms duration. The triggered endplate potentials are abolished in Ca²⁺ -free saline and are blocked by Mn²⁺ ions. Sr²⁺ but not Ba²⁺ can replace Ca²⁺ in supporting transmitter release. Mg²⁺ fails, even in concentrations as high as 32 mm, to affect the amplitude and the shape of the endplate potential but abolishes it when the Ca²⁺ concentration is reduced to 0.2 mm. 2 Despite the large amplitude of the triggered endplate potential in the presence of 4-aminopyridine and tetrodotoxin, repetitive stimulation up to 10 Hz causes only a small decline in amplitude of successive endplate potentials. However, in the presence of (+)-tubocurarine or gallamine, repetitive nerve stimulation produces a marked decline in successive endplate potential amplitude. The fall is counteracted when evoked transmitter release is reduced in the presence of 0.2 mm Ca²⁺. The results suggest that in the presence of 4-aminopyridine such large amounts of transmitter are released that even during repetitive stimulation (5 to 10 Hz) endplate potentials are of maximal amplitude. 3 4-Aminopyridine causes a parallel shift to the right of the dose-response curve to Mg²⁺ for blockade of nerve impw/se-evoked transmitter release (in the absence of tetrodotoxin). A similar parallel shift occurs in the presence of tetraethylammonium and guanidine. 4 It is concluded that 4-aminopyridine increases transmitter release by enhancing the transport efficacy for Ca²⁺ across the nerve terminal membrane during nerve terminal depolarization.