Electrical activity induced by nitric oxide in canine colonic circular muscle

2002 ◽  
Vol 282 (1) ◽  
pp. G123-G129 ◽  
Author(s):  
K. D. Keef ◽  
U. Anderson ◽  
K. O'Driscoll ◽  
S. M. Ward ◽  
K. M. Sanders
Keyword(s):  
Nitric Oxide ◽  
Circular Muscle ◽  
Cyclopiazonic Acid ◽  
Muscle Layer ◽  
Slow Waves ◽  
Potential Oscillations ◽  
Carbonyl Cyanide ◽  
Mitochondrial Uncouplers ◽  
Cells Of Cajal ◽  
Membrane Potential Oscillations

Nitric oxide generates slow electrical oscillations (SEOs) in cells near the myenteric edge of the circular muscle layer, which resemble slow waves generated by interstitial cells of Cajal (ICCs) at the submucosal edge of this muscle. The properties of SEOs were studied to determine whether these events are similar to slow waves. Rapid frequency membrane potential oscillations (MPOs; 16 ± 1 cycles/min and 9.6 ± 0.2 mV) were recorded from control muscles near the myenteric edge. Sodium nitroprusside (0.3 μM) reduced MPOs and initiated SEOs (1.3 ± 0.3 cycles/min and 13.4 ± 1.4 mV amplitude). SEOs were abolished by the guanylate cyclase inhibitor 1H-[1,2,4]-oxadiazolo-[4,3-a]-quinoxaline-1-one (10 μM). MPOs were abolished by nifedipine (1 μM), whereas SEO frequency increased and the amount of depolarization decreased. BAY K 8644 (1 μM) prolonged SEOs and reduced their frequency. SEOs were abolished by Ni2+ (0.5 mM), low Ca2+ solution (0.1 mM Ca2+), cyclopiazonic acid (10 μM), and the mitochondrial uncouplers antimycin (10 μM) and carbonyl cyanide p-trifluoromethoxyphenylhydrazone (1 μM). Oligomycin (10 μM) was without effect. These effects are similar to those described for colonic slow waves. Our results suggest that nitric oxide-induced SEOs are similar in mechanism to slow waves, an activity not previously thought to be generated by myenteric pacemakers.

Electrical and mechanical interactions between the muscle layers of canine proximal colon

1990 ◽  
Vol 258 (3) ◽  
pp. G484-G491 ◽  
Author(s):  
P. J. Sabourin ◽  
Y. J. Kingma ◽  
K. L. Bowes
Keyword(s):  
Membrane Potential ◽  
Circular Muscle ◽  
Longitudinal Direction ◽  
Proximal Colon ◽  
Slow Waves ◽  
The Other ◽  
Potential Oscillations ◽  
Circular Layer ◽  
Longitudinal Layer ◽  
Membrane Potential Oscillations

Electrical and mechanical interactions between the two smooth muscle layers of canine colon have been studied using a dual sucrose gap apparatus. Muscle samples were dissected into an L-shape, with one leg cut in the circular direction and the other cut in the longitudinal direction. Longitudinal muscle was removed from the circular leg and circular muscle was removed from the longitudinal leg. The bend of the L contained both layers. The activity of the two layers was studied simultaneously under basal conditions, after stimulation by neostigmine and carbachol, and in the presence of tetrodotoxin. Interactions were more common after stimulation and were marked by modification of one layer's mechanical and electrical activity during increased activity in the other layer. Two patterns were commonly observed. First, during a burst of membrane potential oscillations and spike potentials in the longitudinal layer, slow waves in the circular layer developed spike potentials and some slow waves were also prolonged. Second, during a slow-wave cycle in the circular layer, the amplitude of membrane potential oscillations in the longitudinal layer was increased with an associated increase in the incidence of spike potentials. These interactions were associated with contractions of increased strength, which were similar in both layers. All interactions continued after nerve-conduction blockade by tetrodotoxin.

scholarly journals ICC pacing mechanisms in intact mouse intestine differ from those in cultured or dissected intestine

2004 ◽  
Vol 286 (4) ◽  
pp. G653-G662 ◽  
Author(s):  
Geoffrey Boddy ◽  
Alicia Bong ◽  
WooJung Cho ◽  
E. E. Daniel
Keyword(s):  
Calcium Release ◽  
Circular Muscle ◽  
Cyclopiazonic Acid ◽  
Regulatory Control ◽  
Intact Mouse ◽  
Carbonyl Cyanide ◽  
Mouse Intestine ◽  
Similarities And Differences ◽  
Cells Of Cajal ◽  
Mitochondrial Uncoupler

Pacing of mouse intestine is driven by spontaneous activity of a network of interstitial cells of Cajal in the myenteric plexus (ICC-MP). So far, highly dissected circular muscle (CM) strips from control and mutant mice lacking ICC-MP and isolated, cultured ICC from newborn control mice were used to analyze its properties. Using intact circular and longitudinal segments of intestine, we recently reported that there were both significant similarities and differences between pacing studied in segments and from isolated, dissected tissues. Here, we report additional similarities and differences in our model from those in highly reduced systems. Similar to cultured or dissected intestine, blockade of sarcoplasmic-endoplasmic reticulum Ca2+ pumps with thapsigargin or cyclopiazonic acid reduced pacing frequency, but thapsigargin was less effective than in isolated, cultured ICC. Moreover, inhibition of inositol 1,4,5-trisphosphate (IP3) receptors with xestospongin C, a putative inhibitor of IP3 receptors, failed to affect pacing but successfully blocked increased pacing frequency by phorbol ester. 2-Aminoethoxy-diphenylborate, a putative blocker of IP3-mediated calcium release, caused a significant decrease in the amplitude and frequency of contractions. The mitochondrial uncoupler carbonyl cyanide p-trifluormethoxyphenylhydrazone blocked pacing and KCl-induced contractions at a concentration of 1 μM. The cyclic nucleotide agonists sodium nitroprusside (SNP), forskolin, and 8-bromo-cGMP inhibited pacing in CM. In longitudinal muscle (LM), SNP and forskolin had little effect on pacing. Furthermore, dibutyryl-cAMP did not affect pacing in CM or LM. These results suggest that pacing in intact intestine is under partly similar regulatory control as in more reduced systems. However, pacing in intact intestine is not affected by xestospongin C, which abolishes pacing in isolated, cultured ICC and exhibits attenuated responses to thapsigargin. Also, major differences between LM and CM suggest a separate pacemaker may drive LM.

Boundary cells between longitudinal and circular layers: essential for electrical slow waves in cat intestine

1986 ◽  
Vol 250 (3) ◽  
pp. G287-G294 ◽  
Author(s):  
N. Suzuki ◽  
C. L. Prosser ◽  
V. Dahms
Keyword(s):  
Interstitial Cells Of Cajal ◽  
Circular Muscle ◽  
Muscle Layer ◽  
Interstitial Cells ◽  
Opposite Polarity ◽  
Slow Waves ◽  
Blue Staining ◽  
Cells Of Cajal ◽  
Two Sides ◽  
Different Levels

Electrical slow waves were recorded by intracellular electrodes and by quasi-intracellular pressure and suction electrodes from muscle fibers at different levels in edgewise preparations of cat jejunum. Simultaneous recordings from longitudinal and circular muscle layers showed similar resting potentials from either muscle layer near the boundary zone, and lower resting potentials in cells of circular muscle near the submucosa. Slow waves were maximal in amplitude at the boundary between the two layers and spread electrotonically away from the boundary in both layers. Bipolar recordings were of opposite polarity on the two sides of the boundary. Amplitudes of slow waves from inner circular fibers were significantly lower than from outer circular fibers. Small strips of each muscle layer were prepared with or without the attached interstitial cells of Cajal plexus as identified by methylene blue staining. Either muscle layer showed slow waves from regions where interstitial cells of Cajal (ICC) were observed after the recording. No slow waves were recorded from either layer from regions where ICC were not observed. Strips containing ICC but not strips lacking ICC could be driven electrically. Since blocking of neurons does not abolish slow waves and since regions of muscle lacking ICC do not have slow waves, it is concluded that the interstitial cells (ICC-I) are most likely the boundary elements essential for slow waves in either layer of intestinal muscle.

In vitro microelectrode study of the electrical properties of smooth muscle in equine ileum

2001 ◽  
Vol 149 (23) ◽  
pp. 707-711 ◽  
Author(s):  
N. P. H. Hudson ◽  
I. G. Mayhew ◽  
G. T. Pearson
Keyword(s):  
Smooth Muscle ◽  
Membrane Potential ◽  
Smooth Muscle Cells ◽  
Longitudinal Muscle ◽  
Muscle Cells ◽  
Muscle Layer ◽  
Potential Oscillations ◽  
Longitudinal Muscle Layer ◽  
Membrane Potential Oscillations

Intracellular microelectrode recordings were made from smooth muscle cells in cross-sectional preparations of equine ileum, superfused in vitro. Membrane potential oscillations and spike potentials were recorded in all preparations, but recordings were made more readily from cells in the longitudinal muscle layer than from cells in the circular layer. The mean (se) resting membrane potential (RMP) of smooth muscle cells in the longitudinal muscle layer was -51.9 (1.2) mV, and the membrane potential oscillations in this layer had a mean amplitude of 4.8 (0.4) mV, a frequency of 9.0 (0.1) cycles per minute and a duration of 5.8 (0.2) seconds. The membrane potential oscillations were preserved in the presence of tetrodotoxin. A waxing and waning pattern of membrane potential oscillation activity was observed. Nifedipine abolished the spiking contractile activity of the smooth muscle, did not abolish the membrane potential oscillations but did alter their temporal characteristics.

Ultrastructural localization of nitric oxide synthase in canine small intestine and colon

1994 ◽  
Vol 266 (4) ◽  
pp. C981-C989 ◽  
Author(s):  
I. Berezin ◽  
S. H. Snyder ◽  
D. S. Bredt ◽  
E. E. Daniel
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Substance P ◽  
Circular Muscle ◽  
Ultrastructural Localization ◽  
Muscle Layer ◽  
Immunogold Staining ◽  
Nitric Oxide Release ◽  
Granular Vesicles ◽  
Oxide Synthase

The ultrastructural distribution and subcellular localization of nitric oxide synthase (NOS) immunoreactivity and its possible colocalization with vasoactive intestinal polypeptide (VIP) and substance P in the muscularis externa in canine ileum and colon were studied by using polyclonal antisera raised against VIP, substance P, and cerebellar NOS. Immunogold staining, with or without silver enhancement, was carried out directly on ultrathin sections using single and two-faced double immunogold methods. NOS immunoreactivity was observed in nerve profiles in myenteric plexus and circular muscle layer. Immunoreactivity was occasionally detected in smooth muscle cells and interstitial cells of Cajal. The double immunostaining revealed NOS and VIP in the same nerve varicosities but never in the same organelles. NOS was localized in electron-dense material of undetermined nature, whereas VIP was associated with large granular vesicles. Substance P and NOS were never found in the same nerves. These results indicate that NOS is present in the enteric nerves containing VIP but in different organelles and that nitric oxide release probably does not occur by an exocytotic mechanism.

Pacemaker potentials generated by interstitial cells of Cajal in the murine intestine

2005 ◽  
Vol 288 (3) ◽  
pp. C710-C720 ◽  
Author(s):  
Yoshihiko Kito ◽  
Sean M. Ward ◽  
Kenton M. Sanders
Keyword(s):  
Interstitial Cells Of Cajal ◽  
Circular Muscle ◽  
Muscle Cells ◽  
Interstitial Cells ◽  
Slow Waves ◽  
Pacemaker Activity ◽  
Dependent Manner ◽  
Plateau Potential ◽  
Pacemaker Potentials ◽  
Cells Of Cajal

Pacemaker potentials were recorded in situ from myenteric interstitial cells of Cajal (ICC-MY) in the murine small intestine. The nature of the two components of pacemaker potentials (upstroke and plateau) were investigated and compared with slow waves recorded from circular muscle cells. Pacemaker potentials and slow waves were not blocked by nifedipine (3 μM). In the presence of nifedipine, mibefradil, a voltage-dependent Ca2+ channel blocker, reduced the amplitude, frequency, and rate of rise of upstroke depolarization (d V/d tmax) of pacemaker potentials and slow waves in a dose-dependent manner (1–30 μM). Mibefradil (30 μM) changed the pattern of pacemaker potentials from rapidly rising, high-frequency events to slowly depolarizing, low-frequency events with considerable membrane noise (unitary potentials) between pacemaker potentials. Caffeine (3 mM) abolished pacemaker potentials in the presence of mibefradil. Pinacidil (10 μM), an ATP-sensitive K+ channel opener, hyperpolarized ICC-MY and increased the amplitude and d V/d tmax without affecting frequency. Pinacidil hyperpolarized smooth muscle cells and attenuated the amplitude and d V/d tmax of slow waves without affecting frequency. The effects of pinacidil were blocked by glibenclamide (10 μM). These data suggest that slow waves are electrotonic potentials driven by pacemaker potentials. The upstroke component of pacemaker potentials is due to activation of dihydropyridine-resistant Ca2+ channels, and this depolarization entrains pacemaker activity to create the plateau potential. The plateau potential may be due to summation of unitary potentials generated by individual or small groups of pacemaker units in ICC-MY. Entrainment of unitary potentials appears to depend on Ca2+ entry during upstroke depolarization.

Expression and function of KCNH2 (HERG) in the human jejunum

2003 ◽  
Vol 284 (6) ◽  
pp. G883-G895 ◽  
Author(s):  
A. M. Farrelly ◽  
S. Ro ◽  
B. P. Callaghan ◽  
M. A. Khoyi ◽  
N. Fleming ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Interstitial Cells Of Cajal ◽  
Circular Muscle ◽  
Slow Waves ◽  
Enteric Neurons ◽  
Longitudinal Smooth Muscle ◽  
Low Concentrations ◽  
Pair Sequence ◽  
And Function ◽  
Cells Of Cajal

Previous studies suggest that ether-a-go-go related gene (ERG) KCNH2 potassium channels contribute to the control of motility patterns in the gastrointestinal tract of animal models. The present study examines whether these results can be translated into a role in human gastrointestinal muscles. Messages for two different variants of the KCNH2 gene were detected: KCNH2 V1 human ERG (HERG) (28) and KCNH2 V2 (HERGUSO) (13). The amount of V2 message was greater than V1 in both human jejunum and brain. The base-pair sequence that gives rise to domains S3– S5 of the channel was identical to that previously published for human KCNH2 V1 and V2. KCNH2 protein was detected immunohistochemically in circular and longitudinal smooth muscle and enteric neurons but not in interstitial cells of Cajal. In the presence of TTX (10−6 M), atropine (10−6M). and l-nitroarginine (10−4 M) human jejunal circular muscle strips contracted phasically (9 cycles/min) and generated slow waves with superimposed spikes. Low concentrations of the KCNH2 blockers E-4031 (10−8 M) and MK-499 (3 × 10−8 M) increased phasic contractile amplitude and the number of spikes per slow wave. The highest concentration of E-4031 (10−6 M) produced a 10–20 mV depolarization, eliminated slow waves, and replaced phasic contractions with a small tonic contracture. E-4031 (10−6 M) did not affect [14C]ACh release from enteric neurons. We conclude that KCNH2 channels play a fundamental role in the control of motility patterns in human jejunum through their ability to modulate the electrical behavior of smooth muscle cells.

Excitatory and inhibitory neural regulation of canine pyloric smooth muscle

1990 ◽  
Vol 259 (1) ◽  
pp. G125-G133 ◽  
Author(s):  
F. Vogalis ◽  
K. M. Sanders
Keyword(s):  
Action Potentials ◽  
Slow Component ◽  
Circular Muscle ◽  
Muscle Layer ◽  
Slow Waves ◽  
Cross Sectional ◽  
Intrinsic Innervation ◽  
Circular Layer ◽  
Neuromuscular Apparatus ◽  
Excitatory Junction Potentials

Studies were performed to characterize the intrinsic innervation of the circular muscle layer of the canine pylorus. Cross-sectional strips of muscle were studied with intracellular recording techniques, and junction potentials were elicited with transmural nerve stimulation. Neurally mediated responses were recorded from cells at several points through the thickness of the circular layer. Excitatory junction potentials (EJPs) increased and inhibitory junction potentials (IJPs) decreased in amplitude with distance from the myenteric border of the circular muscle. Atropine blocked EJPs throughout the circular layer, demonstrating that excitatory inputs are primarily cholinergic. The gradient in IJP amplitude persisted after blockade of EJPs. Three components of IJPs were identified: 1) a fast, apamin-sensitive component that reached a peak and decayed within approximately 1 s; 2) a slower, apamin-insensitive component that reached a peak within 800 ms but decayed slowly over 5 s; and 3) a very slow component that reached a maximum in 7-10 s. Junctional potentials affected the pattern of myogenic electrical activity. Transmural stimulation could evoke premature slow waves in the myenteric portion of the circular layer but when excitatory inputs were blocked, IJPs greatly reduced the amplitude of slow waves. EJPs elicited action potentials in submucosal portion of circular muscles, and IJPs hyperpolarized these cells. The influence of intrinsic nerves on contractile patterns of pyloric muscles was also characterized. These data demonstrate that a neuromuscular apparatus exists within the gastroduodenal junction for 1) local regulation of slow waves and 2) independent control of the myenteric and submucosal regions of the circular layer.

Selective accumulation of methylene blue by interstitial cells of Cajal in canine colon

1993 ◽  
Vol 264 (1) ◽  
pp. G64-G73 ◽  
Author(s):  
L. W. Liu ◽  
L. Thuneberg ◽  
E. E. Daniel ◽  
J. D. Huizinga
Keyword(s):  
Methylene Blue ◽  
Interstitial Cells Of Cajal ◽  
Three Dimensional ◽  
Circular Muscle ◽  
Muscle Cells ◽  
Muscle Layer ◽  
Interstitial Cells ◽  
Resting Membrane Potential ◽  
Selective Staining ◽  
Cells Of Cajal

The network of interstitial cells of Cajal (ICC) at the submucosal surface of the canine colon was selectively stained by incubation with 15-50 microM methylene blue for 30-45 min. The network was composed of regularly scattered ICC cell bodies interconnected by long processes. Circular muscle cells were unstained. Staining of neurons was limited to one or two axons within bundles. The ICC network had a thickness of a single cell, since no overlapping of ICC cell bodies was observed. The ICC network connected the circular muscle cells at the submucosal surface across the septa which circumferentially divided the circular muscle into lamellae. Methylene blue at 50 microM slightly decreased the resting membrane potential and increased the duration of slow waves, leading to an increase in the force of phasic contractions, with no significant influence on other slow-wave parameters. Methylene blue produced neither electrophysiological nor mechanical effects on circular muscle preparations from which the submuscular ICC network was removed, indicating that the excitatory effects of methylene blue on the full-thickness circular muscle layer were mediated by ICC. In summary, the three-dimensional aspects of the submuscular ICC network can be visualized after selective staining by methylene blue. This staining does not affect physiological characteristics of smooth muscle cells.

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