title: Slow synaptic transmission in myenteric AH neurons from the inflamed guinea pig ileum.
abstract: We investigated the effect of inflammation on slow synaptic transmission in myenteric neurons in the guinea pig ileum. Inflammation was induced by the intraluminal injection of trinitrobenzene sulfonate, and tissues were taken for in vitro investigation 6-7 days later. Brief tetanic stimulation of synaptic inputs (20 Hz, 1 s) induced slow excitatory postsynaptic potentials (EPSPs) in 49% and maintained postsynaptic excitation that lasted from 27 min to 3 h in 13% of neurons from the inflamed ileum. These neurons were classified electrophysiologically as AH neurons; 10 were morphological type II neurons, and one was type I. Such long-term hyperexcitability after a brief stimulus is not encountered in enteric neurons of normal intestine. Electrophysiological properties of neurons with maintained postsynaptic excitation were similar to those of neurons with slow EPSPs. Another form of prolonged excitation, sustained slow postsynaptic excitation (SSPE), induced by 1-Hz, 4-min stimulation, in type II neurons from the inflamed ileum reached its peak earlier but had lower amplitude than that in control. Unlike slow EPSPs and similar to SSPEs, maintained excitation was not inhibited by neurokinin-1 or neurokinin-3 receptor antagonists. Maintained postsynaptic excitation was not influenced by PKC inhibitors, but the PKA inhibitor, H-89, caused further increase in neuronal excitability. In conclusion, maintained excitation, observed only in neurons from the inflamed ileum, may contribute to the dysmotility, pain, and discomfort associated with intestinal inflammation.
authors: Dept. of Physiology, The Univ. of Melbourne, Parkville, Victoria, 3010, Australia. knurgali@unimelb.edu.au
authors: Kulmira
authors: K
authors: Nurgali
authors: Trung V
authors: TV
authors: Nguyen
authors: Michelle
authors: M
authors: Thacker
authors: Louise
authors: L
authors: Pontell
authors: John B
authors: JB
authors: Furness
mesh_terms: D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004195:Disease Models, Animal; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials; D005260:Female; D006168:Guinea Pigs; D007079:Ileitis / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D007082:Ileum / Q000294:innervation*; D008297:Male; D009197:Myenteric Plexus / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D009412:Nerve Fibers / Q000187:drug effects / Q000378:metabolism*; D064729:Neurokinin-1 Receptor Antagonists; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D018042:Receptors, Neurokinin-3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects; D013997:Time Factors; D014302:Trinitrobenzenesulfonic Acid
chemical_list: D064729:Neurokinin-1 Receptor Antagonists; D047428:Protein Kinase Inhibitors; D018040:Receptors, Neurokinin-1; D018042:Receptors, Neurokinin-3; D014302:Trinitrobenzenesulfonic Acid; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C