Synaptic plasticity in myenteric neurons of the guinea-pig distal colon: Presynaptic mechanisms of inflammation-induced synaptic facilitation

Eric M. Krauter, David R. Linden, Keith A. Sharkey, Gary M. Mawe

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

The purpose of this study was to investigate the pre- and postsynaptic mechanisms that contribute to synaptic facilitation in the myenteric plexus of the trinitrobenzene sulphonic acid-inflamed guinea-pig distal colon. Intracellular recordings of evoked fast excitatory postsynaptic potentials (fEPSPs) in myenteric S neurons were evaluated, and the density of synaptic terminals was morphometrically analysed by transmission electron microscopy. In inflamed tissue, fEPSPs were reduced to control levels by the protein kinase A (PKA) inhibitor, H89, but H89 did not affect the fEPSPs in control tissue. This PKA activation in inflamed tissue did not appear to involve 5-HT4 receptors because the antagonist/inverse agonist, GR 125487, caused comparable decreases of fEPSPs in both tissues. Inhibition of BK channels with iberiotoxin did not alter the fEPSPs in inflamed tissue, but increased the fEPSPs in control tissue to the amplitude detected in inflamed tissue. During trains of stimuli, run-down of EPSPs was less extensive in inflamed tissue and there was a significant increase in the paired pulse ratio. Depolarizations in response to exogenous neurotransmitters were not altered in inflamed tissue. These inflammation-induced changes were not accompanied by alterations in the pharmacological profile of EPSPs, and no changes in synaptic density were detected by electron microscopy. Collectively, these data indicate that synaptic facilitation in the inflamed myenteric plexus involves a presynaptic increase in PKA activity, possibly involving an inhibition of BK channels, and an increase in the readily releasable pool of synaptic vesicles.

Original languageEnglish (US)
Pages (from-to)787-800
Number of pages14
JournalJournal of Physiology
Volume581
Issue number2
DOIs
StatePublished - Jun 1 2007

ASJC Scopus subject areas

  • Physiology

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