Effect of 4-aminopyridine (4-AP) on the spontaneous activity and neuromuscular junction in the rat colon

• Published in: Pharmacological research Vol. 52; no. 6; pp. 447 - 456
• Main Authors: ALBERTI, E, JIMENEZ, M
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.12.2005
• Subjects: 4-Aminopyridine - pharmacology; Animals; Colon - drug effects; Colon - physiology; Male; Neuromuscular junction; Neuromuscular Junction - drug effects; Neuromuscular Junction - physiology; Nitroarginine - pharmacology; Potassium channel; Potassium Channels - drug effects; Rat colon; Rats; Rats, Sprague-Dawley; Synaptic Transmission - drug effects; Tetrodotoxin - pharmacology; Potassium channel; Neuromuscular junction; Rat colon
• ISSN: 1043-6618; 1096-1186
• DOI: 10.1016/j.phrs.2005.07.002

Two pacemakers are involved in the generation of the spontaneous electrical activity in the rat colon. Slow waves, originated near the submuscular plexus, elicit high frequency contractions whereas low frequency contractions are related to cyclic depolarizations, which might be originated near the Auerbach's plexus. Inhibitory junction potentials (IJPs) in the rat colon show a fast component followed by a sustained NO-mediated hyperpolarization. We have utilised mechanical recordings and intracellular electrophysiology to characterize the effects of 4-AP on spontaneous electrical activity and inhibitory neurotransmission in isolated preparations of rat colon. 4-AP reduced the repolarization of smooth muscle cells and caused a transient (for 4–5 min) depolarization (9.7 ± 3.1 mV; n = 4) and repetitive spikes. The mechanical activity correlated with these electrical changes consisted of a transient increase in tone without cyclic activity followed by long lasting high amplitude cyclic contractions. To avoid smooth muscle cyclic depolarizations, nifedipine 1 μM was added to the perfusion solution. 4-AP 5 mM hyperpolarized (−11.4 ± 2.1 mV, n = 5) the smooth muscle and induced spontaneous IJPs. This effect was not observed when the tissue was preincubated with TTX 1 μM ( n = 7) and L-NNA 1 mM ( n = 4). We conclude that 4-AP inhibits repolarization of smooth muscle cells and induces release of NO from nerve endings. This effect might be due to inhibition of K + channels both in neurons and smooth muscle cells.