Krauter Eric M, Linden David R, Sharkey Keith A, Mawe Gary M
Department of Anatomy and Neurobiology, University of Vermont College of Medicine, Burlington, VT 05405, USA.
J Physiol. 2007 Jun 1;581(Pt 2):787-800. doi: 10.1113/jphysiol.2007.128082. Epub 2007 Mar 15.
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-HT(4) 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.
本研究的目的是探究在三硝基苯磺酸诱发炎症的豚鼠远端结肠肌间神经丛中，导致突触易化的突触前和突触后机制。对肌间S神经元中诱发的快速兴奋性突触后电位（fEPSP）进行细胞内记录评估，并通过透射电子显微镜对突触终末的密度进行形态计量分析。在炎症组织中，蛋白激酶A（PKA）抑制剂H89可将fEPSP降低至对照水平，但H89对对照组织中的fEPSP无影响。炎症组织中的这种PKA激活似乎不涉及5-HT(4)受体，因为拮抗剂/反向激动剂GR 125487在两种组织中均可使fEPSP产生类似程度的降低。用iberiotoxin抑制BK通道不会改变炎症组织中的fEPSP，但会使对照组织中的fEPSP增加至在炎症组织中检测到的幅度。在一连串刺激期间，炎症组织中EPSP的衰减程度较小，且成对脉冲比率显著增加。炎症组织中对外源性神经递质的去极化反应未发生改变。这些炎症诱导的变化并未伴有EPSP药理学特征的改变，并且通过电子显微镜未检测到突触密度的变化。总体而言，这些数据表明，炎症肌间神经丛中的突触易化涉及PKA活性的突触前增加，可能涉及对BK通道的抑制，以及突触小泡易释放池的增加。
