Substance P-mediated membrane currents in voltage-clamped guinea pig inferior mesenteric ganglion cells.

Responses to substance P (SP) and to hypogastric nerve stimulation were recorded from voltage-clamped guinea pig inferior mesenteric ganglion (IMG) neurons, and compared with those to muscarine. Muscarine produced a voltage-dependent inward current accompanied by a reduced input conductance and inhibition of IM a time- and voltage-dependent K+-current (Brown and Adams: Nature 283:673-676, 1980). SP also produced an inward current, accompanied by a fall in input conductance (20 out of 31 cells) or a rise in input conductance (7 out of 31 cells). The fall in input conductance was not accompanied by an inhibition of M-current (unlike frog ganglia: Adams et al.: British Journal of Pharmacology 79:330-333, 1983) or an inhibition of the inward rectifier current (unlike globus pallidus neurons: Stanfield et al.: Nature 315:498-501, 1985). Repetitive hypogastric nerve stimulation (10-20 Hz, 2-10 s) produced a slow inward postsynaptic current lasting 1-3 min, with decreases or increases of input conductance matching those produced by SP. The postsynaptic current did not show a consistent or reproducible change in amplitude on varying the holding potential between -90 and -25 mV. It is concluded that SP and hypogastric stimulation produce complex and variable changes in ionic conductance in IMG neurons.