Apamin-resistant post-stimulus hyperpolarization in the circular muscle of the guinea-pig ileum

Transmural nerve stimulation of the guinea-pig ileum in the presence of atropine at 30°C has been found to produce a relatively brief (duration ∼ 1 s) inhibitory junction potential (IJP) followed by a longer lasting depolarization [1]. When short volleys of stimuli (e.g. 3 pulses, 0.5 ms, 10 Hz) were applied to this tissue, it was noted that the post-stimulus depolarization consisted of at least two distinct phases [2]. The first of these phases, which we called fast post-stimulus depolarization, peaked about 1–1.5 s following the stimulus, whereas the second phase (slow post-stimulus depolarization) peaked about 2–3 s later [2]. After prolonged exposure to substance P (5 × 10 −7 M for > 15 min) the first depolarizing phase was abolished, whereas the second depolarizing phase appeared to be enhanced [4]. In the earlier series of experiments [1], using single stimuli, we observed that the bee-venom neurotoxin apamin [3] abolished the IJP and only a single depolarizing junction potential remained. The time-to-peak of this non-cholinergic excitatory junction potential correlated with the time-to-peak of the initial fast depolarizing response observed when volleys of stimuli were used. In the present series of experiments we have re-examined the effects of apamin on the membrane potential responses following short volleys of stimuli and also the effects of prolonged exposure to substance P in the presence of apamin. We report here, that, following abolition of the IJP by exposure to apamin, prolonged exposure to substance P abolished the fast post-stimulus depolarization and revealed a slow hyperpolarizing response.