Effect of 4-aminopyridine on release of noradrenaline from the perfused cat spleen by nerve stimulation.

1. 4-aminopyridine (4-AP, 1 mM) increased noradrenaline (NA) output from the perfused cat spleen at 5 Hz by about fivefold. Enhancement of NA release by 4-AP was reversible. Output of NA induced by potassium was not affected. 2. NA output was doubled at low concentrations (0.1--0.3 mM) of 4-AP, but maximal effect was obtained at 1--3 mM. At 10 mM, it induced spontaneous release of NA which was insensitive to calcium. 3. Insignificant outputs obtained at 5 Hz in 0.1 and 0.3 mM calcium-Krebs solution were markedly enhanced by 4-AP. 4-AP enhanced release at all calcium concentrations up to 5 mM, but maximum output was obtained at 2.5 mM. 4. 4-AP at pH 8.5 was more effective in enhancing NA release than at pH 7.4. 5. 4-AP increased the recovery of intra-arterially infused NA from the control 26 to 47%. 6. 4-AP did not affect release of catecholamines (CA) from the perfused cat adrenal gland by acetylcholine (ACh). 7. It is suggested that 4-AP inactivates potassium current in sympathetic nerves and prolongs the duration of the action potential, thereby allowing a greater influx of calcium ions into the neurone to enhance release of NA.