Neuronal plasticity in the enteric nervous system motor pathways
The details of the mechanisms underlying neurotransmission within the enteric nervous system are not yet known. Acetylcholine acting on nicotinic receptors mediates the majority of fast synaptic transmission between enteric neurons, however, recent studies suggest that the peristaltic motor pattern can occur during nicotinic receptor blockade. The aim of this thesis was to determine if electrical stimulation of the enteric nerves improved recovery during nicotinic blockade. Two segments of proximal ileum measuring 5-7cm were extracted from guinea pigs of either sex and positioned in an organ bath. Each segment was cannulated and the peristaltic pressure threshold was determined by step-wise increases of the intraluminal pressure from the oral end while pressure recordings were made from the aboral end. Parameters of the peristaltic motor pattern were compared in electrically stimulated and non-electrically stimulated preparations using ANOVA with a repeated measures post-hoc test. Video recordings were made throughout the experiment to detect changes in luminal diameter. The peristaltic pressure threshold was taken as the pressure at which four consecutive propulsive contractions were observed. Nicotinic receptor blockade using hexamethonium or mecamylamine inhibited peristalsis. 6 out of 20 preparations showed almost full recovery with electrical stimulation at the oral end in the presence of hexamethonium. Peristalsis also showed some recovery when electrical stimuli were applied in the presence of muscarinic blockade or IKCa2+ channel blockade. A combination of ligand-gated ion channel blockers did not prevent the recovery seen following electrical stimulation. Anterograde propulsive contractions were observed and recovery enhanced when electrical stimulation was applied at the aboral end of the intestinal segment. The findings of the present study suggest that electrical stimulation improves the recovery of the peristaltic motor pattern in the presence of nicotinic receptor blockade. The mechanism of recovery does not rely on ACh acting at muscarinic receptors, 5-HT or ATP acting at 5-HT3 or P2X receptors (respectively), but may have depended upon an increased excitability of enteric neurons. Thus, neuronal plasticity of the enteric nervous system is highly adaptable and able to compensate for inhibition of multiple receptors in peristaltic motor pathways.
Neurotransmission, Enteric nervous system, Synaptic transmission, Peristaltic motor pattern, Nicotinic receptor blockade, Peristaltic pressure threshold, Hexamethonium, Mecamylamine inhibited peristalsis, IKCa2+, Peristaltic motor pathways
Networked Digital Library of Theses and Dissertations