Characteristics of mucosally projecting myenteric neurones in the guinea-pig proximal colon

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Abstract

  • 1Using retrograde tracing with 1,1′-didodecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI) in combination with electrophysiological and immunohistochemical techniques we determined the properties of the putative intrinsic primary afferent myenteric neurones with mucosal projections in the guinea-pig proximal colon.
  • 2Eighty-four out of eighty-five DiI-labelled myenteric neurones were AH neurones with a late after-hyperpolarization. Thirty-three per cent of them exhibited atropine- and tetrodotoxin-resistant spontaneously occurring hyperpolarizing potentials (SHPs) during which the membrane resistance and excitability decreased.
  • 3DiI-labelled AH neurones had multipolar Dogiel type II morphology, primarily of the dendritic type. Sixty-one per cent of the neurones were immunoreactive for choline acetyltransferase (ChAT) and calbindin (Calb) and 23% were ChAT positive but Calb negative.
  • 4DiI-labelled neurones did not receive fast excitatory postsynaptic potentials but 94% (34/36) received slow excitatory postsynaptic potentials (sEPSPs). The neurokinin-3 (NK-3) agonist (MePhe7)-NKB but not the NK-1 agonist [(SAR9,Met(O2)11]-SP mimicked this response. The NK-3 receptor antagonist SR 142801 (1 μm) significantly decreased the amplitude and duration of the sEPSPs; the NK-1 receptor antagonist CP-99,994 (1 μm) was ineffective. Atropine (0.5 μm) increased the duration but not the amplitude of the sEPSPs.
  • 5Microejection of 100 mM sodium butyrate onto the neurones induced in 90% of the DiI-labelled neurones a transient depolarization associated with an increased excitability. In neurones with SHPs sodium butyrate evoked, additionally, a late onset hyperpolarization. Perfusion of 0.1-10 mM sodium butyrate induced a dose-dependent increase in neuronal excitability. Sodium butyrate was ineffective when applied directly onto the mucosa.
  • 6Mucosally projecting myenteric neurones of the colon are multipolar AH neurones with NK-3-mediated slow EPSPs and somal butyrate sensitivity.

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