SUMMARY1. Intracellular membrane potential recordings were made from circular smooth muscle cells of the guinea-pig ileum in the presence of atropine (1 #M) and nifedipine (01I,tM) at 30 'C.2. Perfusion with adenosine triphospate (ATP, 100 /LM) and vasoactive intestinal peptide (VIP, 2 ,SM) resulted in membrane hyperpolarizations of 6-4 + 0 3 and 6'8 + 03 mV, respectively. Picospritzes of ATP (10 mm in pipette) and VIP (100 tim in pipette) resulted in membrane hyperpolarizations of 6-9 + 04 and 6-3 + 04 mV, respectively.3. The ATP-induced hyperpolarizations were antagonized by ac, ,3-methylene ATP desensitization (100 ,tM for 30 min) and the ATP antagonist Reactive Blue 2 (200 /tM), but were unaffected by the VIP antagonist VIP 10-28 (1 JiM).4. The VIP-induced hyperpolarizations were antagonized by VIP 10-28, but unaffected by a, ,-methylene ATP desensitization and Reactive Blue 2.5. A single pulse of transmural nerve stimulation (2 ms, 15 mA) resulted in an inhibitory junction potential (IJP) that reached a maximal amplitude of 12-9 + 0-5 mV at 378 + 20 ms from the stimulus. This fast IJP was abolished by apamin (2 /zM) or tetrodotoxin (1 pM), antagonized by a, fl-methylene ATP desensitization or Reactive Blue 2, but unaffected by VIP 10-28.6. In the presence of apamin (1 fM), four pulses of transmural stimulation (2 ms, 20 Hz, 15 mA) resulted in an IJP that reached a maximal amplitude of 4-8 + 0-2 mV at 14 + 0-1 s from the stimulus. This slow IJP was antagonized by tetrodotoxin (1 /LM) or VIP 10-28 (1 /bM), augmented by Reactive Blue 2 (200 jm), and unaffected by ax, ,J-methylene ATP desensitization.7. These findings provide evidence that both ATP and VIP are inhibitory neurotransmitters in the circular muscle layer of the ileum and that ATP may be the neurotransmitter responsible for the fast IJP and VIP the neurotransmitter responsible for the slow IJP.MS 9154

We examined the role of peripheral cholinergic and noncholinergic mechanisms in esophageal peristalsis. Intramural nerve elements in rings of circular muscle from six different levels of the opossum esophagus were stimulated transmurally so as to cause neurally mediated muscle contractions. Stimulus frequency was varied from 2 to 40 Hz. An increase in stimulus frequency caused an increase in latencies of contractions in rings from distal esophageal sites and a decrease in latencies in rings from proximal sites. This resulted in a marked slowing of the calculated peristaltic speed. Increasing stimulus frequency also caused an increase in duration and amplitude of contractions. These effects were reversed by atropine (0.1 ,uM), suggesting that higher stimulus frequencies recruited more cholinergic nerves. In the presence of atropine, increasing the stimulus frequency caused an increase in latencies of contraction at all sites, suggesting that increasing stimulation frequency applied to noncholinergic nerves causes an increase in latencies of contraction at all sites. The results of this study indicate that both noncholinergic and cholinergic nerves play a role in the peripheral mechanism of esophageal peristalsis. Cholinergic nerve stimulation reduces the latency and enhances the amplitude and duration of contractions seen with noncholinergic nerve stimulation alone. The influence of cholinergic innervation is most prominent proximally and decreases distally along the smooth muscle portion of the esophagus. This peripherally located gradient of cholinergic innervation plays an important role in determining the speed and amplitude of esophageal peristalsis.The act of swallowing is associated with a peristaltic wave of esophageal contractions. This peristaltic activity in the skeletal muscle portion of the esophagus is due to sequential activation of lower muscle neurons in the vagal nuclei (1, 2). However, in the smooth muscle portion, this peristaltic activity may be due to peripheral intramural mechanisms (1, 2). This is evidenced by studies showing the following. (i) After bilateral vagotomy, balloon distension in the esophagus causes peristalsis in the smooth muscle portion (secondary peristalsis) (2,3). (ii) In vitro transmural stimulation of circular muscle strips from different esophageal levels shows that strips from more proximal sites have shorter latencies of contraction than strips from more distal sites (4). (iii) Electrical stimulation of the peripheral end of the decentralized vagus nerve causes peristaltic contractions in the smooth muscle portion of the esophagus (5, 6). In addition, the speed and polarity of peristalsis can be modified by altering the parameters of the electrical stimuli applied to the decentralized vagal nerves (6), thereby demonstrating that peripheral mechanisms possess the ability to modulate the speed of esophageal peristalsis.The nature of the nerves involved in the peripheral regulation of peristalsis is not fully known. It has been suggested by some investigators t...

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Junction potentials were recorded from circular muscle cells of the guinea pig ileum at various sites oral and anal to a transmural stimulus in the presence of atropine, apamin, and substance P antagonism (desensitization) at 30 degrees C. A short train of pulses produced an inhibitory junction potential (slow IJP), which preceded an excitatory junction potential (slow EJP). The slow IJP was observed up to 56.4 +/- 2.9 mm oral and 65.4 +/- 2.2 mm anal to the stimulus. The slow EJP was observed up to 50.4 +/- 1.9 mm oral and 58.3 +/- 2.1 mm anal to the stimulus. Hexamethonium (400 microM) decreased the amplitudes of the slow IJP and slow EJP at all sites. After hexamethonium, the slow IJP was observed up to 37.3 +/- 2.3 mm oral and 39.8 +/- 2.1 mm anal to the stimulus and the slow EJP was 44.2 +/- 2.5 mm oral and 43.3 +/- 2.6 mm anal to the stimulus. The slow IJP and slow EJP were associated with an increase and decrease in membrane resistance, respectively. Conditioning depolarizations of the circular muscle cells reduced the amplitudes of the slow IJP and slow EJP. Both were abolished at a membrane potential of approximately -25 mV. Conditioning hyperpolarizations increased the amplitude of both the slow IJP and slow EJP. Ionic substitution experiments with low external chloride solution (12.4 mM) resulted in an immediate increase in slow IJP and slow EJP amplitudes, whereas more prolonged perfusion resulted in a significant decrease in slow IJP and slow EJP amplitudes. 4,4'-Diisothiocyanostilbene-2,2'-disulfonic acid (400 microM) resulted in decreases in slow IJP and slow EJP amplitudes. These results suggest that the slow IJP and slow EJP are due to a decrease and increase in membrane chloride conductance, respectively. The noncholinergic neural pathways responsible for the slow IJP and slow EJP extend approximately 40 mm orally and anally along the longitudinal axis of the guinea pig ileum.