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Synaptic facilitation and enhanced neuronal excitability in the submucosal plexus during experimental colitis in guinea‐pig
Author(s) -
Lomax Alan E.,
Mawe Gary M.,
Sharkey Keith A.
Publication year - 2005
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2005.084285
Subject(s) - hexamethonium , excitatory postsynaptic potential , neurotransmission , neuroscience , electrophysiology , enteric nervous system , myenteric plexus , postsynaptic potential , acetylcholine , inhibitory postsynaptic potential , submucous plexus , neural facilitation , chemistry , biology , endocrinology , medicine , receptor , immunohistochemistry , biochemistry
Intestinal secretion is regulated by submucosal neurones of the enteric nervous system. Inflammation of the intestines leads to aberrant secretory activity; therefore we hypothesized that the synaptic and electrical behaviours of submucosal neurones are altered during colitis. To test this hypothesis, we used intracellular microelectrode recording to compare the excitability and synaptic properties of submucosal neurones from normal and trinitrobenzene sulphonic acid (TNBS)‐inflamed guinea‐pig colons. Inflammation differentially affected the electrophysiological characteristics of the two functional classes of submucosal neurones. AH neurones from inflamed colons were more excitable, had shorter action potential durations and reduced afterhyperpolarizations. Stimulus‐evoked fast and slow excitatory postsynaptic potentials (EPSPs) in S neurones were larger during colitis, and the incidence of spontaneous fast EPSPs was increased. In control preparations, fast EPSPs were almost completely blocked by the nicotinic receptor antagonist hexamethonium, whereas fast EPSPs in inflamed S neurones were only partially inhibited by hexamethonium. In inflamed tissues, components of the fast EPSP in S neurones were sensitive to blockade of P2 X and 5‐HT 3 receptors while these antagonists had little effect in control preparations. Control and inflamed S neurones were equally sensitive to brief application of acetylcholine, ATP and 5‐HT, suggesting that synaptic facilitation was due to a presynaptic mechanism. Immunoreactivity for 5‐HT in the submucosal plexus was unchanged by inflammation; this indicates that altered synaptic transmission was not due to anatomical remodelling of submucosal nerve terminals. This is the first demonstration of alterations in synaptic pharmacology in the enteric nervous system during inflammation.