Gwynne Rachel M, Bornstein Joel C
Department of Physiology, University of Melbourne, Parkville, Victoria 3010, Australia.
Am J Physiol Gastrointest Liver Physiol. 2009 Jul;297(1):G179-86. doi: 10.1152/ajpgi.90700.2008. Epub 2009 Apr 30.
Slow excitatory postsynaptic potentials (EPSPs) in enteric neurons arise from diverse sources, but which neurotransmitters mediate specific types of slow EPSPs is unclear. We investigated transmitters and receptors mediating slow EPSPs in myenteric neurons evoked by electrical stimulation of the mucosa in guinea pig small intestine. Segments of ileum or jejunum were dissected to allow access to the myenteric plexus adjacent to intact mucosa, in vitro. AH and S neurons were impaled with conventional intracellular electrodes. Trains of stimuli delivered to the mucosa evoked slow EPSPs in AH neurons that were blocked or depressed by the neurokinin-1 (NK1) tachykinin antagonist SR140333 (100 nM) in 10 of 11 neurons; the NK3 tachykinin receptor antagonist SR142801 (100 nM) had no effect on slow EPSPs in seven of nine AH neurons. Single pulses to the mucosa evoked fast EPSPs and slow depolarizations in S neurons. The depolarizations were divided into intermediate (durations 300-900 ms) or slow (durations 1.3-9 s) EPSPs. The slow EPSPs were blocked by pyridoxal phosphate-6-axophenyl-2-4-disulfonic acid (30 microM, N = 3) or the specific P2Y(1) antagonist MRS 2179 (10 microM, N = 6) and were predominantly in anally projecting S neurons that were immunoreactive for nitric oxide synthase (NOS). In contrast, intermediate EPSPs were predominantly evoked in NOS-negative neurons; these were abolished by MRS 2179 (N = 8). Thus activation of pathways running from the mucosa excites three different types of slow EPSP in myenteric neurons, which are mediated by either a tachykinin (NK1, AH neurons) or a purine nucleotide (P2Y(1), S neurons).
肠神经元中的慢兴奋性突触后电位（EPSP）有多种来源，但尚不清楚哪种神经递质介导特定类型的慢EPSP。我们研究了豚鼠小肠黏膜电刺激诱发的肌间神经丛神经元中慢EPSP的递质和受体。解剖回肠或空肠段，以便在体外接触完整黏膜相邻的肌间神经丛。用传统细胞内电极刺入AH和S神经元。向黏膜施加的一串刺激在AH神经元中诱发慢EPSP，在11个神经元中的10个中，神经激肽-1（NK1）速激肽拮抗剂SR140333（100 nM）可阻断或抑制该慢EPSP；NK3速激肽受体拮抗剂SR142801（100 nM）对9个AH神经元中的7个的慢EPSP没有影响。向黏膜施加单个脉冲在S神经元中诱发快速EPSP和缓慢去极化。去极化分为中间型（持续时间300 - 900毫秒）或慢型（持续时间1.3 - 9秒）EPSP。慢EPSP被磷酸吡哆醛 - 6 - 轴苯基 - 2,4 - 二磺酸（30 microM，N = 3）或特异性P2Y(1)拮抗剂MRS 2179（10 microM，N = 6）阻断，且主要出现在对一氧化氮合酶（NOS）免疫反应阳性的向肛投射的S神经元中。相比之下，中间型EPSP主要在NOS阴性神经元中诱发；这些EPSP被MRS 2179消除（N = 8）。因此，从黏膜发出的通路激活可在肌间神经丛神经元中激发三种不同类型的慢EPSP，它们分别由速激肽（NK1，AH神经元）或嘌呤核苷酸（P2Y(1)，S神经元）介导。
