Non-cholinergic synaptic potentials mediated by lumbar colonic nerve in the guinea-pig inferior mesenteric ganglion in vitro

Abstract

Non-cholinergic slow synaptic potentials mediated by the lumbar colonie nerve have been investigated using an in vitro preparation of the guinea-pig inferior mesenteric ganglion attached to a distal colonie segment. Non-cholinergic potential responses to colonie nerve stimulation, colonie distension and chemical activation of sensory afferents were recorded intracellularly from neurons in the inferior mesenteric ganglion. Electrical stimulation of the lumbar colonie nerve produced either a slow excitatory postsynaptic potential, or a slow inhibitory postsynaptic potential followed by a slow excitatory postsynaptic potential. The extrapolated reversal potential of the slow excitatory postsynaptic potential was in the range of 0 to − 20 mV and that of the slow inhibitory postsynaptic potential was −90 to 110 mV. The slow excitatory postsynaptic potential and the slow inhibitory postsynaptic potential were reversibly abolished by perfusion of the ganglion with tetrodotoxin (1 μM), or perfusion with low calcium (200 μM), high magnesium (12 mM) containing solution. Capsaicin (1 μM) evoked a reversible depolarization of inferior mesenteric ganglion cells after which desensitization occurred and the slow excitatory postsynaptic potential was abolished but the slow inhibitory postsynaptic potential was enhanced in amplitude and prolonged in duration. Bath application of substance P (2 μM) evoked a prolonged depolarization of inferior mesenteric ganglion neurons, during which the slow excitatory postsynaptic potential but not the slow inhibitory postsynaptic potential was abolished. Distensions of the colon to pressures in the range of 2–25 cm of water produced a stimulus graded non-cholinergic slow depolarization which was occasionally followed by a late slow hyperpolarization. Both types of response were abolished by tetrodotoxin. Capsaicin (2 μM), acetylcholine (1 μM) or potassium (60 mM) application to the colon produced a smooth muscle contraction accompanied by a slow depolarization of inferior mesenteric ganglion neurons. These data suggest that the colonie nerve contains mixed populations of non-cholinergic afferent fibres which are involved in the generation of either a slow excitatory postsynaptic potential or slow inhibitory postsynaptic potential in the inferior mesenteric ganglion. Fibres mediating the slow excitatory postsynaptic potential were capsaicin-sensitive and are probably C-fibre primary afferents releasing a tachykinin-like neurotransmitter in the inferior mesenteric ganglion. Fibres mediating the slow inhibitory postsynaptic potential were not capsaicin-sensitive primary afferents and the identity of their inhibitory transmitter is unknown. It is likely that both types of afferent fibres are mechanosensory and can be activated by distension or contraction of the colon.