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

1. Using retrograde tracing with 1,1'-didodecyl-3,3,3',3'-tetramethylindoca rbocyanine perchlorate (DiI) in combination with electrophysiological and i mmunohistochemical techniques eve determined the properties of the putative intrinsic primary afferent myenteric neurones with mucosal projections in the guinea-pig proximal colon. 2. Eighty-four out of eighty-five DiI-labelled myenteric neurones were BH n eurones with a late after-hyperpolarization. Thirty-three per cent of them exhibited atropine- and tetrodotoxin-resistant spontaneously occurring hype rpolarizing potentials (SHPs) during which the membrane resistance and exci tability decreased. 3. DiI-labelled AK neurones had multipolar Dogiel type II morphology, prima rily of the dendritic type. Sixty-one per cent of the neurones were immunor eactive for choline acetyltransferase (ChAT) and calbindin (Calb) and 23% w ere ChAT positive but Calb negative. 4. DiI-labelled neurones did not receive fast excitatory postsynaptic poten tials but 94% (34/36) received slow excitatory postsynaptic potentials (sEP SPs). The neurokinin-3 (NK-3) agonist (MePhe(7))-NKB but not the NK-1. agon ist [(SAR(9),Met(O-2)(11)]-SP mimicked this response. The NK-3 receptor ant agonist SR 142801 (1 mu M) significantly decreased the amplitude and durati on of the sEPSPs; the NK-1. receptor antagonist CP-99,994 (1 mu M) was inef fective. Atropine (0.5 mu M) increased the duration but not the amplitude o f the sEPSPs. 5. Microejection 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, addi tionally, a late onset hyperpolarization. Perfusion of 0.1-10 mM sodium but yrate induced a close-dependent increase in neuronal excitability. Sodium b utyrate was ineffective when applied directly onto the mucosa. 6. Mucosally projecting myenteric neurones of the colon are multipolar AK n eurones with NK-3-mediated slow EPSPs and somal butyrate sensitivity.