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  • Title: 4-Aminopyridine and evoked transmitter release from motor nerve endings.
    Author: Illes P, Thesleff S.
    Journal: Br J Pharmacol; 1978 Dec; 64(4):623-9. PubMed ID: 31961.
    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 Ca(2+)-free saline and are blocked by Mn(2+) ions. Sr(2+) but not Ba(2+) can replace Ca(2+) in supporting transmitter release. Mg(2+) 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 Ca(2+) 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 Ca(2+). 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 prallel shift to the right of the dose-response curve to Mg(2+) for blockade of nerve impulse-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 Ca(2+) across the nerve terminal membrane during nerve terminal depolarization.
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