scholarly journals Molecular and functional characterization of Kv7 K+ channel in murine gastrointestinal smooth muscles

2009 ◽  
Vol 297 (1) ◽  
pp. G107-G115 ◽  
Author(s):  
Thomas A. Jepps ◽  
Iain A. Greenwood ◽  
James D. Moffatt ◽  
Kenton M. Sanders ◽  
Susumu Ohya
Keyword(s):  
Contractile Activity ◽  
Functional Characterization ◽  
Smooth Muscles ◽  
Circular Muscle ◽  
Distal Colon ◽  
Muscle Layer ◽  
K Channel ◽  
Neuronal Membrane ◽  
Gi Tract ◽  
Membrane Excitability

Members of the Kv7 voltage-gated K+ channel family are important determinants of cardiac and neuronal membrane excitability. Recently, we and others have shown that Kv7 channels are also crucial regulators of smooth muscle activity. The aim of the present study was to assess the Kv7 expression in different parts of the murine gastrointestinal (GI) tract and to assess their functional roles by use of pharmacological agents. Of KCNQ/Kv7 members, both KCNQ4/Kv7.4 and KCNQ5/Kv7.5 genes and proteins were the most abundantly expressed Kv7 channels in smooth muscles throughout the GI tract. Immunohistochemical staining also revealed that Kv7.4 and Kv7.5 but not Kv7.1 were expressed in the circular muscle layer of the colon. In segments of distal colon circular muscle exhibiting spontaneous phasic contractions, the nonselective Kv7 blockers XE991 and linopirdine increased the integral of tension. Increases in the integral of tension were also observed under conditions of neuronal blockade. Similar effects, although less marked, were observed in the proximal colon. As expected, the Kv7.1-selective blocker chromanol 293B had no effect in either type of segment. These data show that Kv7.x especially Kv7.4 and Kv7.5 are expressed in different regions of the murine gastrointestinal tract and blockers of Kv7 channels augment inherent contractile activity. Drugs that selectively block Kv7.4/7.5 might be promising therapeutics for the treatment of motility disorders such as constipation associated with irritable bowel syndrome.

Myosin phosphorylation and contraction of feline esophageal smooth muscle

1985 ◽  
Vol 249 (1) ◽  
pp. C9-C14 ◽  
Author(s):  
N. W. Weisbrodt ◽  
R. A. Murphy
Keyword(s):  
Smooth Muscle ◽  
Mechanical Activation ◽  
Smooth Muscles ◽  
Circular Muscle ◽  
Electrical Field Stimulation ◽  
Muscle Layer ◽  
Field Stimulation ◽  
Shortening Velocity ◽  
Myosin Phosphorylation ◽  
Isotonic Shortening

We tested the hypothesis that phosphorylation of the 20,000-Da light chain of myosin (LC 20) is related to mechanical activation of esophageal smooth muscle. Circular muscle layer strips of cat esophagus were taken from the lower esophageal sphincter (LES) and the distal esophageal body (EB). The LES strips developed tone spontaneously, and the EB strips were tonically contracted with carbachol. Both tissues relaxed in response to electrical-field stimulation. Phosphorylation of the LC 20 was determined in tissues quick-frozen during relaxation and during stress redevelopment after cessation of field stimulation. Stress and phosphorylation levels were low after 30 s of field stimulation, and a rapid contraction followed field stimulation. Phosphorylation in the LES increased from 0.043 +/- 0.029 to 0.328 +/- 0.043 mol Pi/mol LC 20 within 10 s after stimulation of the inhibitory nerves was terminated, while stress was still rising rapidly. Phosphorylation in the LES then declined to a steady-state value of 0.162 +/- 0.034 mol Pi/mol LC 20 after 10 min. Isotonic shortening velocities at a constant afterload following a quick release showed changes with time that were proportional to the level of phosphorylation. This was also true for values of maximal shortening velocity estimated for zero external load and for the rate of stress redevelopment after a step shortening. Comparable measurements were made in the carbachol-contracted EB. These results indicate that visceral smooth muscles, which normally function tonically (LES) or phasically (EB), exhibit an initial rapid mechanical activation associated with myosin phosphorylation.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals A Qualitative and Quantitative Study on the Enkephalinergic Innervation of the Pig Gastrointestinal Tract

2000 ◽  
Vol 48 (3) ◽  
pp. 333-343 ◽  
Author(s):  
Christophe Porcher ◽  
Yvon Julé ◽  
Monique Henry
Keyword(s):  
Anal Sphincter ◽  
Neural Control ◽  
Circular Muscle ◽  
Distal Colon ◽  
Muscle Layer ◽  
Intestinal Wall ◽  
Nerve Fibers ◽  
Longitudinal Muscle Layer ◽  
Submucous Plexus ◽  
Qualitative And Quantitative

Enkephalins are involved in neural control of digestive functions such as motility, secretion, and absorption. To better understand their role in pigs, we analyzed the qualitative and quantitative distribution of enkephalin immunoreactivity (ENK-IR) in components of the intestinal wall from the esophagus to the anal sphincter. Immunohistochemical labelings were analyzed using conventional fluorescence and confocal microscopy. ENK-IR was compared with the synaptophysin immunoreactivity (SYN-IR). The results show that maximal ENK-IR levels in the entire digestive tract are reached in the myenteric plexuses and, to a lesser extent, in the external submucous plexus and the circular muscle layer. In the longitudinal muscle layer, ENK-IR was present in the esophagus, stomach, rectum, and anal sphincter, whereas it was absent from the duodenum to the distal colon. In the ENK-IR plexuses and muscle layers, more than 60% of the nerve fibers identified by SYN-IR expressed ENK-IR. No ENK-IR was observed in the internal submucous plexus and the mucosa; the latter was found to contain ENK-IR endocrine cells. These results strongly suggest that, in pigs, enkephalins play a major role in the regulatory mechanisms that underlie the neural control of digestive motility.

Substance P and CGRP mediate motor response of rabbit colon to capsaicin

1990 ◽  
Vol 259 (5) ◽  
pp. G889-G897 ◽  
Author(s):  
E. A. Mayer ◽  
C. B. Koelbel ◽  
W. J. Snape ◽  
V. Eysselein ◽  
H. Ennes ◽  
...  
Keyword(s):  
Substance P ◽  
Longitudinal Muscle ◽  
Contractile Activity ◽  
Circular Muscle ◽  
Muscle Layer ◽  
Inhibitory Effect ◽  
Nerve Fibers ◽  
Repeated Exposure ◽  
Nerve Terminals ◽  
Rabbit Colon

Primary afferent nerve terminals located in the mammalian gut wall may play a role in region-specific modulation of gastrointestinal motility. In the present study, we sought to characterize the effect of neuropeptides released from these afferents by capsaicin (CAP) on contractile activity of smooth muscle from the distal rabbit colon. CAP caused a release of acetylcholine and immunoreactivity for substance P (SP) and calcitonin gene-related peptide (CGRP) from the muscle coat. CAP caused a dose-dependent transient stimulation of longitudinal muscle contractions, followed by prolonged inhibition of spontaneous but not stimulated contractile activity. The initial stimulation was abolished by the SP antagonist spantide and by atropine. The inhibitory effect was reduced by repeated exposure of muscle to CGRP. The effect of CGRP on spontaneous contractions differed between longitudinal and circular muscle. In longitudinal muscle, a stimulation was preceded by a transient inhibition, whereas in circular muscle, only inhibition was seen. Both effects were resistant to tetrodotoxin. Repeated exposure of circular but not longitudinal muscle to CGRP resulted in a disappearance of the peptide's inhibitory effect. Exogenously applied CGRP was only a weak antagonist of contractions stimulated by SP and bethanechol. These findings suggest that in the rabbit colon at least the following two neuropeptides are released from CAP-sensitive nerve fibers: a neurokinin peptide from nerve terminals located within the myenteric plexus and CGRP from terminals probably located within the circular muscle layer.

Colonic motor response to a meal in dogs

1989 ◽  
Vol 257 (5) ◽  
pp. G830-G835 ◽  
Author(s):  
S. K. Sarna ◽  
I. M. Lang
Keyword(s):  
Cycle Length ◽  
Contractile Activity ◽  
Total Duration ◽  
Early Period ◽  
Circular Muscle ◽  
Distal Colon ◽  
Postprandial Period ◽  
Colonic Motor ◽  
Colonic Motor Activity ◽  
The Mean

We investigated the effects of ingestion of a meal on colonic motor activity in six conscious dogs, each instrumented with seven strain-gauge transducers to record circular muscle contractions. A 1,300-kcal meal was given after a 4-h control recording. The post-prandial period of 8 h was subdivided into an early period lasting 2 h and a late period lasting 6 h. The ingestion of the meal did not disrupt the colonic migrating myoelectric complexes (CMMCs) but prolonged their cycle length in the early postprandial period. The cycle length was not different from the control during the late postprandial period. The mean and total duration of contractile activity per hour increased significantly during the early postprandial period in the distal colon but not in the proximal or the middle colon. During the late postprandial period the mean and total duration of contractile activity per hour increased significantly throughout the colon. Giant migrating contractions occurred rarely during the 8-h postprandial period. We conclude that different parts of the colon respond to the ingestion of a meal in different ways. The response also depends on whether the fresh digesta has reached the colon. The late postprandial response is likely to be due to the entry of fresh digesta into the colon.

scholarly journals Impairment and restoration of spontaneous contractile activity of longitudinal smooth muscles in the TNBS-inflamed hamster distal colon

2007 ◽  
Vol 28 (6) ◽  
pp. 301-308 ◽  
Author(s):  
Yam B. GURUNG ◽  
Yasutake SHIMIZU ◽  
Takahiko SHIINA ◽  
Motamed E. MAHMOUD ◽  
Shouichiro SAITO ◽  
...  
Keyword(s):  
Contractile Activity ◽  
Smooth Muscles ◽  
Distal Colon

Generation of spiking activity in circular muscle cells of the canine colon

1987 ◽  
Vol 65 (10) ◽  
pp. 2147-2150 ◽  
Author(s):  
Jan D. Huizinga ◽  
Carlos Barajas-Lopez ◽  
Edwin Chow
Keyword(s):  
Myenteric Plexus ◽  
Contractile Activity ◽  
Extracellular Recording ◽  
Circular Muscle ◽  
Muscle Cells ◽  
Muscle Layer ◽  
Organ Bath ◽  
Force Of Contraction ◽  
Plateau Potential ◽  
Spiking Activity

Spontaneous and current-induced electrical activity was recorded intracellularly to resolve the controversy whether or not the circular muscle layer of the colon generates spiking activity. Particularly in the first hour after mounting the tissue in the organ bath, spikes were recorded at both the submucosal and the myenteric plexus side of the muscle layer. Spikes were seen as part of the slow wave upstroke in the submucosal surface cells, and spikes occurred both at the upstroke potential and superimposed on the plateau potential in myenteric plexus surface cells. Spikes increased the force of contraction. The study supports earlier claims using extracellular recording techniques that circular muscle cells generate spiking activity, particularly in the presence of depolarizing stimuli, and that spikes contribute to contractile activity.

Mice lacking the dopamine transporter display altered regulation of distal colonic motility

2000 ◽  
Vol 279 (2) ◽  
pp. G311-G318 ◽  
Author(s):  
Julia K. L. Walker ◽  
Raul R. Gainetdinov ◽  
Allen W. Mangel ◽  
Marc G. Caron ◽  
Michael A. Shetzline
Keyword(s):  
Contractile Activity ◽  
Colonic Motility ◽  
Distal Colon ◽  
Wild Type ◽  
Gi Tract ◽  
Inhibitory Effects ◽  
Motility Index ◽  
Organ Tissue ◽  
Altered Regulation ◽  
Species Specific

The mechanisms by which dopamine (DA) influences gastrointestinal (GI) tract motility are incompletely understood and complicated by tissue- and species-specific differences in dopaminergic function. To improve the understanding of DA action on GI motility, we used an organ tissue bath system to characterize motor function of distal colonic smooth muscle segments from wild-type and DA transporter knockout (DAT −/−) mice. In wild-type mice, combined blockade of D1 and D2 receptors resulted in significant increases in tone (62 ± 9%), amplitude of spontaneous phasic contractions (167 ± 24%), and electric field stimulation (EFS)-induced (40 ± 8%) contractions, suggesting that endogenous DA is inhibitory to mouse distal colonic motility. The amplitudes of spontaneous phasic and EFS-induced contractions were lower in DAT −/− mice relative to wild-type mice. These differences were eliminated by combined D1 and D2 receptor blockade, indicating that the inhibitory effects of DA on distal colonic motility are potentiated in DAT −/− mice. Motility index was decreased but spontaneous phasic contraction frequency was enhanced in DAT −/− mice relative to wild-type mice. The fact that spontaneous phasic and EFS-induced contractile activity were altered by the lack of the DA transporter suggests an important role for endogenous DA in modulating motility of mouse distal colon.

Characterization of the properties of canine colonic smooth muscle in culture

1993 ◽  
Vol 265 (5) ◽  
pp. C1433-C1442 ◽  
Author(s):  
M. J. Rogers ◽  
S. M. Ward ◽  
M. A. Horner ◽  
K. M. Sanders ◽  
B. Horowitz
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscles ◽  
Potential Gradient ◽  
Circular Muscle ◽  
Electrical Field Stimulation ◽  
Muscle Layer ◽  
Enteric Neurons ◽  
Resting Potential ◽  
Northern Analysis ◽  
Functional Components

We have developed and characterized an organ culture system that maintains the viability of colonic smooth muscles. Morphological, mechanical, electrical, and molecular properties of cultured canine colonic circular muscles were determined. Strips of circular muscle were cultured for up to 6 days. The smooth muscle phenotype was retained during culture; muscles contracted to agonists and responded to electrical field stimulation, suggesting that intrinsic nerves also survived in culture. Morphological analysis showed identifiable smooth muscle cells, enteric neurons, and interstitial cells, but some alterations in ultrastructure were also observed. Mechanical responses to acetylcholine suggested that the muscles developed supersensitivity during the culture period. The resting membrane potentials of cells near the submucosal surface of the circular muscle layer decreased from -82 mV on day 0 to -55 mV on day 3. Similar changes in the resting potential gradient occur when colonic muscles are treated with inhibitors of the Na(+)-K(+)-ATPase. Resting potentials of day 3 muscles remained constant in low external K+ (0.1 mM), suggesting little contribution of the pump to resting potential. Northern analysis of RNA from muscles cultured up to 6 days showed that the alpha 2-isoform of the pump decreased. The data suggest that organ-cultured strips of smooth muscle may provide a useful tool for evaluating electrical and mechanical events in conjunction with molecular analysis of functional components.

Studies in vivo and in vitro on effects of PGE2 on colonic motility in rabbits

1992 ◽  
Vol 262 (1) ◽  
pp. G23-G29 ◽  
Author(s):  
R. Burakoff ◽  
W. H. Percy
Keyword(s):  
Colonic Motility ◽  
Circular Muscle ◽  
Distal Colon ◽  
Muscle Layer ◽  
Distal Region ◽  
Mechanical Activity ◽  
Experimental Conditions ◽  
Motor Effects

Prostaglandins (PG) of the E series are synthesized throughout the gastrointestinal tract, and their elevated levels have been reported in many diarrheal states, including inflammatory bowel disease. It is already known that PGE2 has region-specific and muscle layer-specific effects in different areas of the intestine. The aim of this study was to evaluate possible dose-related motor effects of PGE2 on rabbit proximal and distal colon both in vivo and in vitro. We found that, in the proximal colon in vivo, PGE2 caused inhibition of myoelectric and mechanical activity at low doses but at higher doses caused marked excitation. Under the same experimental conditions, PGE2 caused only excitation in the distal colon, a phenomenon associated with an increase in antegrade contractions and diarrhea. In vitro, PGE2 caused excitation of both proximal and distal colonic longitudinal muscle and relaxation of the circular muscle. Its actions, however, were much more pronounced in the distal region. It is concluded that PGE2 has profound effects on colonic motility that are concentration dependent and that differ with the region of the colon under study. Furthermore, the evidence also suggests that elevated PGE2 levels in disease states may play a significant role in abnormal colonic motility and may facilitate the onset of diarrhea.

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