The effect of 4-aminopyridine on acetylcholine release

Abstract

The effect of 2-, and 4-aminopyridine (4-APYR) on the release mechanism of acetylcholine (ACh) from the nerve terminals of the Auerbach plexus-longitudinal muscle preparation of the guinea-pig ileum, suspended in eserinized Krebs' solution, was investigated. 2- and 4-APYR increased the release of ACh from the nerve terminals at rest and at both low and high frequency stimulation. The enhanced ACh release was found to be due to increased volley output. At lower frequency of stimulation, potentiation of ACh release was much higher than at higher rate of stimulation. 4-APYR was able to increase ACh release in the absence of [Ca2+]o. However, when a Ca-chelating agent, EDTA, was also added to the Ca-free Krebs' solution, 4-APYR was entirely ineffective. The depression of ACh release induced by Mg-excess was completely antagonized by 4-APYR. Tetrodotoxin (TTX) prevented augmentation of ACh release by 4-APYR. It is suggested that 4-APYR lowers the demand of nerve terminals for [Ca2+]o required for the excitation-secretion coupling process. The presence of a low concentration [Ca2+]o, however, is essential for the action of 4-APYR.

4-Aminopyridine Toxicity: a Case Report and Review of the Literature

“…4-AP enhances the release of acetylcholine from nerve endings and has been shown to increase dopamine transmission in rat striatum [3][4][5][6][7]. Furthermore, it is frequently used as an experimental agent to induce seizures.…”

T wave changes persisting after ventricular pacing in canine heart are altered by 4-aminopyridine but not by lidocaine. Implications with respect to phenomenon of cardiac 'memory'.

“…4-Aminopyridine facilitates synaptic transmission by increasing calciumdependent transmitter release in a variety of tissues. 32,33 There are conflicting reports of its cardiac effects in vivo. Paskov et a134 found no cardiovascular effects of 4-aminopyridine, whereas others describe positive35,36 or negative37 chronotropic and inotropic responses, depending on the cardiac preparation and species used.…”

Mechanisms of nicotine-induced cutaneous vasodilation and sweating in young adults: roles for KCa, KATP, and KVchannels, nitric oxide, and prostanoids

“…However, 4-aminopyridine has been shown to augment acetylcholine release from the nerve terminals (Vizi et al 1977). Since nicotine-induced sweating is mediated through sudomotor axon reflex induced increase in acetylcholine release (Schlereth et al 2005), nicotinic sweating (and possibly nicotinic cutaneous vasodilation) may have been augmented with 4-aminopyridine administration in this study.…”