Effect of Substance P on Non-Cholinergic Post-Stimulus Depolarization of the Circular Smooth Muscle of the Guinea Pig Ileum

Abstract

The membrane potential of the cells of the circular layer of the guinea-pig ileum was recorded in vitro at 30^°C in the presence of atropine (1.4 x 10⁻⁶ M) using intracellular microelectrodes. Following transmural (TM) nerve stimulation the inhibitory junction potential (i.j.p.) was followed by two separate depolarizing responses. The first of these (fast post-stimulus depolarization, FPSD) peaked 1.5 sec after the stimulus, whilst the second (slow post-stimulus depolarization,SPSD) peaked 3–4 sec after the stimulus (Bywater and Taylor, 1). After prolonged exposure ( > 10 min) of the tissue to substance P (SP: 10⁻⁷ to 10⁻⁶ M), the circular muscle cells were depolarized by 6.4 ± 1.1 mV and their membrane resistance increased by 50 to 100%. At this time, following TM nerve stimulation, the amplitude of the i.j.p. was increased by 20 to 50%, FPSD was abolished whereas SPSD was generally unaffected. In some preparations however, the amplitude of SPSD was increased and it reached threshold for action potential generation. In the latter preparations and in the absence of stimulation, the membrane potential occasionally showed regular oscillations of approximately 10 mV in amplitude every 5 to 8 sec. Hyperpolarization did not restore FPSD indicating that its abolition was not a secondary effect due to the depolarization of the tissue by SP. Moreover, during an hyperpolarization of approximately 20 mV, a transient large depolarization was revealed during the phase of SPSD. Assuming that prolonged exposure to SP desensitizes the tissue to that substance, these results indicate that SP may be involved in the genesis of FPSD. SPSD probably results from a different mechanism and shows some similarities with slow waves.