Comprehensive Physiology Wiley Online Library

Neuromuscular transmission in the gastrointestinal tract

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Abstract

The sections in this article are:

1 Electrophysiology of Neuromuscular Transmission
1.1 Effector Structure
1.2 Autonomic Neuromuscular Junction
1.3 Recording Techniques
1.4 Ion Permeability and Conductance Changes in Effector Smooth Muscle Membrane
2 Adrenergic Neuromuscular Transmission in the Gastrointestinal Tract
2.1 Projection of Adrenergic Neurons Within the Muscle Coat
2.2 Action of Adrenergic Nerves
2.3 Sphincteric Muscles
2.4 Nonsphincteric Muscles
2.5 Adrenergic Neuromodulation
2.6 Sympathetic Cotransmission in the Gastrointestinal Tract
3 Transmission From Inhibitory Nerves
3.1 Inhibitory Junction Potentials
3.2 Projection of Inhibitory Neurons Within the Gut Wall
3.3 Putative Inhibitory Neurotransmitters
4 Transmission From Excitatory Nerves
4.1 Ionic Basis of Excitatory Junction Potentials
4.2 Excitatory Neuromuscular Transmitters
5 Neuromuscular Transmission In Disease States
5.1 Hirschsprung's Disease
5.2 Diabetes Mellitus
5.3 Chronic Constipation and Cathartic Colon
5.4 Slow‐Transit Constipation
5.5 Ulcerative Colitis
5.6 Diverticular Disease
5.7 Irritable Bowel Syndrome
5.8 Crohn's Disease
5.9 Summary
6 Future Directions
Figure 1. Figure 1.

Excitatory junction potentials (EJPs) in rabbit colon circular muscle. Sucrose‐gap recording technique. A: single pulse of electrical field stimulation (arrow) evoked an EJP. B: stimulus strength was raised so that electrical field stimulation (arrow) evoked an action potential.

Figure 2. Figure 2.

Scanning electronic micrograph of single terminal varicose nerve fiber lying over smooth muscle of small intestine of rat. Intestine was pretreated to remove connective tissue components by digestion with trypsin and hydrolysis with HCl. Bar, 3 μm.

From Burnstock , by courtesy of Marcel Dekker, Inc
Figure 3. Figure 3.

Scanning electronic micrograph of myenteric plexus of rat small intestine. Two large ganglia (G) contain neurons, fibroblasts, and glial cells. Underlying and between these is circular muscle coat with smooth muscle cells (M) running vertically. Interstitial cells (asterisks) overlie smooth muscle cells and ganglia and extend processes that have intimate contact with muscle cells and with each other; some of the interstitial cells are also associated with ganglia. Bar, 24 μm.

Micrograph courtesy of T. Komuro
Figure 4. Figure 4.

Nonadrenergic, noncholinergic inhibitory junction potentials (IJPs) recorded in smooth muscles from several species with sucrose‐gap technique. All preparations are from circular muscle layers except those of guinea pig (GP) and human taenia coli, which are longitudinal muscles. Small transients preceding large hyperpolarizations are stimulus artifacts and indicate the point at which intramural nerves were stimulated by electrical field stimulation (single pulse, 0.1–0.5 ms). In rabbit ileum, IJP was evoked at top of slow wave of depolarization. In human, rabbit, and rat preparations and in guinea pig taenia coli, IJPs are monophasic and essentially similar. In guinea pig colon and cecum, IJPs are more complex, with extended phases of repolarization.

Figure 5. Figure 5.

Effect of distension on spontaneous electrical activity of colonic smooth muscle recorded simultaneously at the level of the balloon (EMG 1; EMG, electromyograph) and 2 cm below (EMG 2). At distending point, distension produced a discharge of action potentials, and below the distending point, a hyperpolarization of smooth muscle fibers, which was followed a few seconds later by a discharge of action potentials. Diagram under the EMG indicates position of recording electrodes

From Julé
Figure 6. Figure 6.

Hyperpolarization of colonic smooth muscle evoked by distension recorded simultaneously at 2 cm (EMG 1), 15 cm (EMG 2), and 20 cm (EMG 3) below balloon. Diagram under the EMG indicates position of recording electrodes.

From Julé
Figure 7. Figure 7.

Diagram of excitable membrane. ENa, EK, and ECl:equilibrium potentials for sodium, potassium, and chloride. E, membrane potential. RNa, RK, and RCl: resistance to movement of sodium, potassium, and chloride ions. C, membrane capacity.

From Casteels ; after Hodgkin a)
Figure 8. Figure 8.

Conductance changes of smooth muscle membrane of rabbit ileum and guinea pig gastric antrum during slow‐wave activity. A: rabbit ileum circular muscle. Upper trace, recording of spontaneous slow‐wave activity; middle trace, anelectrotonic potentials were generated by passing constant current pulses (17 μA, 0.2 s per 1 s); tower trace, direction of current was reversed to generate catelectrotonic potentials. Amplitude of electrotonic potentials is smaller at peak of slow waves than at resting membrane potential, indicating an increased conductance at peak. B: guinea pig gastric antrum circular muscle. Order of traces is as in A. Constant current pulses (10 μA, 0.5 s per 2 s) were applied. As in rabbit ileum, electrotonic potentials are smaller at peak of slow waves than at resting membrane potential.

Figure 9. Figure 9.

Simultaneous demonstration of neurons and adrenergic axons in myenteric plexus. Neurons were stained for NADH‐diaphorase by incubating tissue at room temperature in saline‐glucose solution containing nitro blue tetrazolium and NADH. It was then dried and exposed to formaldehyde vapor and illuminated with ultraviolet light using a bright‐field condenser. Neurons appear dark (arrows); adrenergic axons appear white. Adrenergic axons form a plexus around neurons. Bar, 50 μm.

From Costa and Furness , courtesy of Chapman & Hall, Ltd
Figure 10. Figure 10.

Effect of phentolamine (1.5 mg/kg) on sphincteric circular muscle response evoked by hypogastric nerve stimulation on acute preparation. A: control. B‐D: recordings respectively 2.5, 4, and 9 min after phentolamine (1.5 mg/kg iv). Voltage calibration: 1 mV in A‐C; 0.5 mV in D. Responses to nerve stimulation (black dots; 3 shocks, 20 Hz, 1 ms, 10 V) were not followed by a period of activity of smooth muscle fibers. Time constant of amplifiers: 2.5 s.

From Bouvier and Gonella
Figure 11. Figure 11.

Effect of lumbar sympathetic nerve stimulation on mechanical response of isolated rabbit colon to pelvic (parasympathetic) nerve stimulation (black dots; 2–10 Hz, 5 s). Control response to pelvic stimulation (P) is illustrated first, and frequency of stimulation of lumbar sympathetic nerves (25 s, 1–20 Hz), during which parasympathetic nerves were stimulated, is given below each response.

From Gillespie and Khoyi
Figure 12. Figure 12.

Sucrose‐gap recording of membrane potential changes in smooth muscle of guinea pig taenia coli in presence of atropine (0.3 μM) and guanethidine (4 μM). Transmural field stimulation (0.5 ms, 0.033 Hz, 8 V) evoked transient hyperpolarizations or inhibitory junction potentials, which were followed by rebound depolarizations. Tetrodotoxin (TTX, 3 μM) added to the superfusing Krebs solution (applied at arrow) rapidly abolished response to transmural field stimulation.

From Burnstock
Figure 13. Figure 13.

Diagrams of projections of inhibitory junction potential (IJP)‐producing neurons along (A) and around circumference (B) of small intestine. Cell bodies of IJP‐producing neurons are in ganglia of myenteric plexus (M.p.). Their axons project for varying distances, up to 30 mm, in anal direction and then enter circular muscle (C.m.), where they join circumferentially arranged nerve bundles that supply this muscle. Majority of inputs of IJP neurons to muscle come from short projections that supply the muscle beneath the ganglia in which the cell bodies are located and for up to ∼2 mm anally. Longest projections run for up to 30 mm anally from cell body of origin; over final 12 mm of their axons they provide collaterals to circular muscle. In a circumferential direction (B), axons run for some distance in myenteric plexus and then run in circular muscle. Each axon supplies up to 11 mm, i.e., about half of the circumference. Diagrams are not to scale. L.m., longitudinal muscle; M, mucosa.

From Bornstein et al.
Figure 14. Figure 14.

Effect of trypsin on biphasic response to nerve stimulation. A: biphasic response to nerve stimulation in Krebs solution (KS). B: inhibitory response blocked by trypsin (10 U/ml). Blockade by trypsin suggests that a neuropeptide such as vasoactive intestinal polypeptide is involved in inhibitory response.

From Angel et al.
Figure 15. Figure 15.

Effect of antiserum raised against vasoactive intestinal polypeptide (VIP) on inhibitory response to nerve stimulation. Two traces are superimposed. Trace labeled KS + VIP antiserum (KS, Krebs solution) obtained 6 min after adding VIP antiserum (1:75 dilution). Period of nerve stimulation is indicated. Near‐abolition of inhibitory response in VIP antiserum solution.

From Angel et al.
Figure 16. Figure 16.

Typical tracings showing effect of nucleotide pyrophosphatase (0.25 U/ml) on relaxation of rat duodenum induced by ATP (1 mM), field stimulation (0.1 Hz; middle trace), and norepinephrine (1 μM; NA, noradrenaline). Black dots, application of single electrical pulse (60 V, 2 ms), which stimulates nonadrenergic, noncholinergic inhibitory nerves.

From Manzini et al.
Figure 17. Figure 17.

Typical tracings showing effect of reactive blue 2 (0.1 mM) on relaxation of rat duodenum induced by ATP (1 mM), field stimulation (0.1 Hz), and norepinephrine (1 μM; NA, noradrenaline). Black dots, application of single electrical pulse (60 V, 2 ms), which stimulates nonadrenergic, noncholinergic inhibitory nerves.

From Manzini et al.
Figure 18. Figure 18.

Typical tracings showing effect of reactive blue 2 (RB2) on single electrical pulse‐evoked (supramaximal voltage; 0.5 ms) inhibitory junction potentials (IJPs). Downward deflection, hyperpolarization. Reactive blue 2 produces slight depolarization. Table shows effect of reactive blue 2 on IJPs elicited with single pulses of field stimulation in rat cecum (n = 5).

From Manzini et al.
Figure 19. Figure 19.

Relationships between amplitudes of excitatory junction potentials (EJPs) and inhibitory junction potentials (IJPs) and membrane potential levels of rabbit rectum longitudinal muscle cells. Vr, estimated reversal potential levels for EJPs or IJPs obtained from extrapolation of linear relationship between amplitude and membrane potential, n, Number of replicates.

From Suzuki et al. , © 1979, reprinted with permission from Pergamon Journals, Ltd
Figure 20. Figure 20.

Relationships between amplitudes of nonadrenergic, noncholinergic junction potentials and membrane potential levels for 3 different cells for excitatory junction potentials (EJP, solid symbols) and inhibitory junction potentials (IJP, open symbols), respectively. Atropine (1 μM) and guanethidine (10 μM) were present during and for at least 20 min before the experiments to block cholinergic transmission and adrenergic transmission, respectively.

From Bauer and Kuriyama
Figure 21. Figure 21.

Effect of substance P on guinea pig ileum preparation. Tips of 2 floating electrodes were placed on stripped longitudinal muscle and exposed circular muscle at determined distance from line of reflection of longitudinal muscle strip. Peristalsis was induced by raising pressure of intestinal segment by elevating the reservoir and then opening a stopcock, introducing saline into the lumen. Pressure was released by opening a 2nd stopcock and returning the bottle to its original level. Longitudinal muscle strip was allowed to contract isometrically. Upper 2 traces, electrical activity of circular muscle (c) and longitudinal muscle ; bottom trace, periods of application of pressure change (p). A: control. B: 15 min after adding atropine (100 nM), which remained present in C‐E. C: 3 min after adding substance P, circular muscle contraction was increased. D, E: 8 and 13 min, respectively, after addition of substance P. Circular muscle activity was blocked in E. F: 30 min after washing out atropine and substance P. Pressure increases of 4 cm H2O stimulated peristalsis. Bars, 5 s and 50 μV.

From Yokoyama and North
Figure 22. Figure 22.

Effect of prolonged exposure to substance P on slow poststimulus depolarization in guinea pig ileum circular muscle. A, B: recordings show membrane potential changes after 2nd, 3rd, and 4th stimulus volleys (3 pulses, 0.6 ms, 10 Hz, 30 mA, every 7 s). A: in control solution each inhibitory junction potential was followed by fast and slow poststimulus depolarizations. B: after 20‐min exposure to substance P (5 × 10−7 M), fast poststimulus depolarization was abolished but slow poststimulus depolarization was increased in amplitude and initiated action potentials. C: in presence of substance P (but in absence of nerve stimulation), oscillations of membrane potential occurred every 5–8 s and these could trigger action potentials.

From Niel et al.
Figure 23. Figure 23.

Excitatory junction potentials (EJPs) recorded from same smooth muscle cell of chick rectum in response to intramural nerve stimulation (upper trace) and Remak's nerve stimulation (lower trace). EJPs are nonadrenergic, noncholinergic. Stimulation of Remak's nerve stimulates neurons preganglionic to those that produce the EJP, because this effect is blocked by hexamethonium. Intramural nerve stimulation excites postganglionic neurons and is not sensitive to hexamethonium.

From Komori and Ohashi
Figure 24. Figure 24.

Effects of field stimulations on membrane potential of longitudinal muscle cell in ganglionic (a, b) or aganglionic segments (c) of human colon, measured with microelectrodes. In a, single field stimulation evoked excitatory junction potentials (EJPs) and repetitive stimulations (3 stimuli at 20 Hz) enhanced amplitude of EJP and triggered action potential. In b1, single or repetitive field stimulations evoked biphasic potential change [initial EJP and following inhibitory junction potential (IJP)]. Values indicate number of stimuli at 20 Hz. In b2, atropine (7 × 10−6 M) abolished initial EJP, separating IJP. In b3, treatment with phentolamine (10−5 M) and propranolol (10−5 M) in presence of atropine (7 × 10−6 M) did not affect amplitude of IJP. Traces b1, b2, and b3 are from the same cell. In c1, in aganglionic segments, multiple field stimulations (>10 stimuli) were needed to evoke EJPs. Amplitude of EJP was dependent on number of stimuli used, and action potential was triggered on EJP when 13 stimuli at 20 Hz were applied. In c2, atropine abolished generation of EJPs, and in presence of atropine, repetitive field stimulations did not evoke any change in membrane potential.

From Kubota et al.
Figure 25. Figure 25.

Effects of field stimulations on membrane potential of circular muscle cell in ganglionic (a, b) or aganglionic segments (c) of human colon, measured with double sucrose‐gap method. Number of stimuli was increased in a stepwise manner from 1 to 9 at 20 Hz. In α1, field stimulations evoked inhibitory junction potentials (IJPs), amplitude of which was increased in proportion to number of stimuli. In α2, tetrodotoxin (3 × 10−7 M) abolished generation of IJPs. Records α1 and α2are continuous. In b1, field stimulations evoked initial excitatory junction potentials (EJPs) followed by IJPs. Amplitudes of EJP and IJP were dependent on number of stimuli, and EJPs triggered action potentials followed by twitch tension developments when a threshold membrane depolarization was reached. In b2, in presence of atropine (7 × 10−6 M), phentolamine (10−6 M), and propranolol (10−6 M), field stimulations evoked IJPs. In b3, tetrodotoxin (3 × 10−7 M) abolished generation of IJPs. Records b1, b2, and b3 are continuous. In c1, in aganglionic segments, field stimulations evoked EJPs with or without action potential but not IJPs. In c2, atropine (7 × 10−6 M) abolished generation of EJPs evoked by field stimulations. Records c1 and c2 are continuous.

From Kubota et al.


Figure 1.

Excitatory junction potentials (EJPs) in rabbit colon circular muscle. Sucrose‐gap recording technique. A: single pulse of electrical field stimulation (arrow) evoked an EJP. B: stimulus strength was raised so that electrical field stimulation (arrow) evoked an action potential.



Figure 2.

Scanning electronic micrograph of single terminal varicose nerve fiber lying over smooth muscle of small intestine of rat. Intestine was pretreated to remove connective tissue components by digestion with trypsin and hydrolysis with HCl. Bar, 3 μm.

From Burnstock , by courtesy of Marcel Dekker, Inc


Figure 3.

Scanning electronic micrograph of myenteric plexus of rat small intestine. Two large ganglia (G) contain neurons, fibroblasts, and glial cells. Underlying and between these is circular muscle coat with smooth muscle cells (M) running vertically. Interstitial cells (asterisks) overlie smooth muscle cells and ganglia and extend processes that have intimate contact with muscle cells and with each other; some of the interstitial cells are also associated with ganglia. Bar, 24 μm.

Micrograph courtesy of T. Komuro


Figure 4.

Nonadrenergic, noncholinergic inhibitory junction potentials (IJPs) recorded in smooth muscles from several species with sucrose‐gap technique. All preparations are from circular muscle layers except those of guinea pig (GP) and human taenia coli, which are longitudinal muscles. Small transients preceding large hyperpolarizations are stimulus artifacts and indicate the point at which intramural nerves were stimulated by electrical field stimulation (single pulse, 0.1–0.5 ms). In rabbit ileum, IJP was evoked at top of slow wave of depolarization. In human, rabbit, and rat preparations and in guinea pig taenia coli, IJPs are monophasic and essentially similar. In guinea pig colon and cecum, IJPs are more complex, with extended phases of repolarization.



Figure 5.

Effect of distension on spontaneous electrical activity of colonic smooth muscle recorded simultaneously at the level of the balloon (EMG 1; EMG, electromyograph) and 2 cm below (EMG 2). At distending point, distension produced a discharge of action potentials, and below the distending point, a hyperpolarization of smooth muscle fibers, which was followed a few seconds later by a discharge of action potentials. Diagram under the EMG indicates position of recording electrodes

From Julé


Figure 6.

Hyperpolarization of colonic smooth muscle evoked by distension recorded simultaneously at 2 cm (EMG 1), 15 cm (EMG 2), and 20 cm (EMG 3) below balloon. Diagram under the EMG indicates position of recording electrodes.

From Julé


Figure 7.

Diagram of excitable membrane. ENa, EK, and ECl:equilibrium potentials for sodium, potassium, and chloride. E, membrane potential. RNa, RK, and RCl: resistance to movement of sodium, potassium, and chloride ions. C, membrane capacity.

From Casteels ; after Hodgkin a)


Figure 8.

Conductance changes of smooth muscle membrane of rabbit ileum and guinea pig gastric antrum during slow‐wave activity. A: rabbit ileum circular muscle. Upper trace, recording of spontaneous slow‐wave activity; middle trace, anelectrotonic potentials were generated by passing constant current pulses (17 μA, 0.2 s per 1 s); tower trace, direction of current was reversed to generate catelectrotonic potentials. Amplitude of electrotonic potentials is smaller at peak of slow waves than at resting membrane potential, indicating an increased conductance at peak. B: guinea pig gastric antrum circular muscle. Order of traces is as in A. Constant current pulses (10 μA, 0.5 s per 2 s) were applied. As in rabbit ileum, electrotonic potentials are smaller at peak of slow waves than at resting membrane potential.



Figure 9.

Simultaneous demonstration of neurons and adrenergic axons in myenteric plexus. Neurons were stained for NADH‐diaphorase by incubating tissue at room temperature in saline‐glucose solution containing nitro blue tetrazolium and NADH. It was then dried and exposed to formaldehyde vapor and illuminated with ultraviolet light using a bright‐field condenser. Neurons appear dark (arrows); adrenergic axons appear white. Adrenergic axons form a plexus around neurons. Bar, 50 μm.

From Costa and Furness , courtesy of Chapman & Hall, Ltd


Figure 10.

Effect of phentolamine (1.5 mg/kg) on sphincteric circular muscle response evoked by hypogastric nerve stimulation on acute preparation. A: control. B‐D: recordings respectively 2.5, 4, and 9 min after phentolamine (1.5 mg/kg iv). Voltage calibration: 1 mV in A‐C; 0.5 mV in D. Responses to nerve stimulation (black dots; 3 shocks, 20 Hz, 1 ms, 10 V) were not followed by a period of activity of smooth muscle fibers. Time constant of amplifiers: 2.5 s.

From Bouvier and Gonella


Figure 11.

Effect of lumbar sympathetic nerve stimulation on mechanical response of isolated rabbit colon to pelvic (parasympathetic) nerve stimulation (black dots; 2–10 Hz, 5 s). Control response to pelvic stimulation (P) is illustrated first, and frequency of stimulation of lumbar sympathetic nerves (25 s, 1–20 Hz), during which parasympathetic nerves were stimulated, is given below each response.

From Gillespie and Khoyi


Figure 12.

Sucrose‐gap recording of membrane potential changes in smooth muscle of guinea pig taenia coli in presence of atropine (0.3 μM) and guanethidine (4 μM). Transmural field stimulation (0.5 ms, 0.033 Hz, 8 V) evoked transient hyperpolarizations or inhibitory junction potentials, which were followed by rebound depolarizations. Tetrodotoxin (TTX, 3 μM) added to the superfusing Krebs solution (applied at arrow) rapidly abolished response to transmural field stimulation.

From Burnstock


Figure 13.

Diagrams of projections of inhibitory junction potential (IJP)‐producing neurons along (A) and around circumference (B) of small intestine. Cell bodies of IJP‐producing neurons are in ganglia of myenteric plexus (M.p.). Their axons project for varying distances, up to 30 mm, in anal direction and then enter circular muscle (C.m.), where they join circumferentially arranged nerve bundles that supply this muscle. Majority of inputs of IJP neurons to muscle come from short projections that supply the muscle beneath the ganglia in which the cell bodies are located and for up to ∼2 mm anally. Longest projections run for up to 30 mm anally from cell body of origin; over final 12 mm of their axons they provide collaterals to circular muscle. In a circumferential direction (B), axons run for some distance in myenteric plexus and then run in circular muscle. Each axon supplies up to 11 mm, i.e., about half of the circumference. Diagrams are not to scale. L.m., longitudinal muscle; M, mucosa.

From Bornstein et al.


Figure 14.

Effect of trypsin on biphasic response to nerve stimulation. A: biphasic response to nerve stimulation in Krebs solution (KS). B: inhibitory response blocked by trypsin (10 U/ml). Blockade by trypsin suggests that a neuropeptide such as vasoactive intestinal polypeptide is involved in inhibitory response.

From Angel et al.


Figure 15.

Effect of antiserum raised against vasoactive intestinal polypeptide (VIP) on inhibitory response to nerve stimulation. Two traces are superimposed. Trace labeled KS + VIP antiserum (KS, Krebs solution) obtained 6 min after adding VIP antiserum (1:75 dilution). Period of nerve stimulation is indicated. Near‐abolition of inhibitory response in VIP antiserum solution.

From Angel et al.


Figure 16.

Typical tracings showing effect of nucleotide pyrophosphatase (0.25 U/ml) on relaxation of rat duodenum induced by ATP (1 mM), field stimulation (0.1 Hz; middle trace), and norepinephrine (1 μM; NA, noradrenaline). Black dots, application of single electrical pulse (60 V, 2 ms), which stimulates nonadrenergic, noncholinergic inhibitory nerves.

From Manzini et al.


Figure 17.

Typical tracings showing effect of reactive blue 2 (0.1 mM) on relaxation of rat duodenum induced by ATP (1 mM), field stimulation (0.1 Hz), and norepinephrine (1 μM; NA, noradrenaline). Black dots, application of single electrical pulse (60 V, 2 ms), which stimulates nonadrenergic, noncholinergic inhibitory nerves.

From Manzini et al.


Figure 18.

Typical tracings showing effect of reactive blue 2 (RB2) on single electrical pulse‐evoked (supramaximal voltage; 0.5 ms) inhibitory junction potentials (IJPs). Downward deflection, hyperpolarization. Reactive blue 2 produces slight depolarization. Table shows effect of reactive blue 2 on IJPs elicited with single pulses of field stimulation in rat cecum (n = 5).

From Manzini et al.


Figure 19.

Relationships between amplitudes of excitatory junction potentials (EJPs) and inhibitory junction potentials (IJPs) and membrane potential levels of rabbit rectum longitudinal muscle cells. Vr, estimated reversal potential levels for EJPs or IJPs obtained from extrapolation of linear relationship between amplitude and membrane potential, n, Number of replicates.

From Suzuki et al. , © 1979, reprinted with permission from Pergamon Journals, Ltd


Figure 20.

Relationships between amplitudes of nonadrenergic, noncholinergic junction potentials and membrane potential levels for 3 different cells for excitatory junction potentials (EJP, solid symbols) and inhibitory junction potentials (IJP, open symbols), respectively. Atropine (1 μM) and guanethidine (10 μM) were present during and for at least 20 min before the experiments to block cholinergic transmission and adrenergic transmission, respectively.

From Bauer and Kuriyama


Figure 21.

Effect of substance P on guinea pig ileum preparation. Tips of 2 floating electrodes were placed on stripped longitudinal muscle and exposed circular muscle at determined distance from line of reflection of longitudinal muscle strip. Peristalsis was induced by raising pressure of intestinal segment by elevating the reservoir and then opening a stopcock, introducing saline into the lumen. Pressure was released by opening a 2nd stopcock and returning the bottle to its original level. Longitudinal muscle strip was allowed to contract isometrically. Upper 2 traces, electrical activity of circular muscle (c) and longitudinal muscle ; bottom trace, periods of application of pressure change (p). A: control. B: 15 min after adding atropine (100 nM), which remained present in C‐E. C: 3 min after adding substance P, circular muscle contraction was increased. D, E: 8 and 13 min, respectively, after addition of substance P. Circular muscle activity was blocked in E. F: 30 min after washing out atropine and substance P. Pressure increases of 4 cm H2O stimulated peristalsis. Bars, 5 s and 50 μV.

From Yokoyama and North


Figure 22.

Effect of prolonged exposure to substance P on slow poststimulus depolarization in guinea pig ileum circular muscle. A, B: recordings show membrane potential changes after 2nd, 3rd, and 4th stimulus volleys (3 pulses, 0.6 ms, 10 Hz, 30 mA, every 7 s). A: in control solution each inhibitory junction potential was followed by fast and slow poststimulus depolarizations. B: after 20‐min exposure to substance P (5 × 10−7 M), fast poststimulus depolarization was abolished but slow poststimulus depolarization was increased in amplitude and initiated action potentials. C: in presence of substance P (but in absence of nerve stimulation), oscillations of membrane potential occurred every 5–8 s and these could trigger action potentials.

From Niel et al.


Figure 23.

Excitatory junction potentials (EJPs) recorded from same smooth muscle cell of chick rectum in response to intramural nerve stimulation (upper trace) and Remak's nerve stimulation (lower trace). EJPs are nonadrenergic, noncholinergic. Stimulation of Remak's nerve stimulates neurons preganglionic to those that produce the EJP, because this effect is blocked by hexamethonium. Intramural nerve stimulation excites postganglionic neurons and is not sensitive to hexamethonium.

From Komori and Ohashi


Figure 24.

Effects of field stimulations on membrane potential of longitudinal muscle cell in ganglionic (a, b) or aganglionic segments (c) of human colon, measured with microelectrodes. In a, single field stimulation evoked excitatory junction potentials (EJPs) and repetitive stimulations (3 stimuli at 20 Hz) enhanced amplitude of EJP and triggered action potential. In b1, single or repetitive field stimulations evoked biphasic potential change [initial EJP and following inhibitory junction potential (IJP)]. Values indicate number of stimuli at 20 Hz. In b2, atropine (7 × 10−6 M) abolished initial EJP, separating IJP. In b3, treatment with phentolamine (10−5 M) and propranolol (10−5 M) in presence of atropine (7 × 10−6 M) did not affect amplitude of IJP. Traces b1, b2, and b3 are from the same cell. In c1, in aganglionic segments, multiple field stimulations (>10 stimuli) were needed to evoke EJPs. Amplitude of EJP was dependent on number of stimuli used, and action potential was triggered on EJP when 13 stimuli at 20 Hz were applied. In c2, atropine abolished generation of EJPs, and in presence of atropine, repetitive field stimulations did not evoke any change in membrane potential.

From Kubota et al.


Figure 25.

Effects of field stimulations on membrane potential of circular muscle cell in ganglionic (a, b) or aganglionic segments (c) of human colon, measured with double sucrose‐gap method. Number of stimuli was increased in a stepwise manner from 1 to 9 at 20 Hz. In α1, field stimulations evoked inhibitory junction potentials (IJPs), amplitude of which was increased in proportion to number of stimuli. In α2, tetrodotoxin (3 × 10−7 M) abolished generation of IJPs. Records α1 and α2are continuous. In b1, field stimulations evoked initial excitatory junction potentials (EJPs) followed by IJPs. Amplitudes of EJP and IJP were dependent on number of stimuli, and EJPs triggered action potentials followed by twitch tension developments when a threshold membrane depolarization was reached. In b2, in presence of atropine (7 × 10−6 M), phentolamine (10−6 M), and propranolol (10−6 M), field stimulations evoked IJPs. In b3, tetrodotoxin (3 × 10−7 M) abolished generation of IJPs. Records b1, b2, and b3 are continuous. In c1, in aganglionic segments, field stimulations evoked EJPs with or without action potential but not IJPs. In c2, atropine (7 × 10−6 M) abolished generation of EJPs evoked by field stimulations. Records c1 and c2 are continuous.

From Kubota et al.
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Charles H. V. Hoyle, Geoffrey Burnstock. Neuromuscular transmission in the gastrointestinal tract. Compr Physiol 2011, Supplement 16: Handbook of Physiology, The Gastrointestinal System, Motility and Circulation: 435-464. First published in print 1989. doi: 10.1002/cphy.cp060113