Effect of substance P on non-cholinergic fast and slow post-stimulus depolarization in the guinea-pig ileum

Membrane potentials were recorded with intracellular electrodes from the circular muscle cells of the guinea-pig ileum, in vitro, in the presence of atropine (1.4 X 10(-6) M) at 30 degrees C. Under such conditions, the preparations did not show any spontaneous activity. Exposure of the tissue to substance P (10(-7)-10(-6)M) for a short period of time (less than 5 min) caused depolarization and action potentials. At this time the membrane resistance appeared to be decreased and after transmural nerve stimulation the fast post-stimulus depolarization, which followed the inhibitory junction potential (IJP), triggered action potentials. After prolonged exposure of the tissue to substance P (greater than 10 min), the contractile activity of the preparation subsided, the membrane potential was decreased by 6.4 +/- 1.1 mV and the membrane resistance was increased; following transmural nerve stimulation, the amplitude of the IJP was increased, the fast post-stimulus depolarization was abolished and the later slow post-stimulus depolarization was enhanced and in some preparations reached threshold for action potential generation. In the latter preparations in the absence of transmural nerve stimulation, the membrane potential occasionally showed regular oscillations of approximately 10 mV in amplitude every 5-8 s. When the tissue was hyperpolarized by anodal current, after prolonged exposure to substance P, the fast post-stimulus depolarization did not return indicating that its abolition was not a secondary effect due to the depolarization of the tissue by substance P.