Excitation-contraction coupling without Ca2+ action potentials in small intestine

1983 ◽  
Vol 244 (5) ◽  
pp. C356-C361 ◽  
Author(s):  
K. M. Sanders

Sensitive mechanical and intracellular electrical recordings showed that phasic contractions occurred in response to electrical slow waves in the absence of Ca2+ action potentials. Drugs that either enhanced or depressed slow waves were used to study the relationship between slow-wave amplitude and the amplitude of the phasic contractions. Acetylcholine (Ach) (10(-8) to 3 X 10(-7) M) increased slow waves and contractions without causing action potentials. When ACh was raised to 10(-6) M, action potentials were elicited and accompanying contractions increased in amplitude by at least a factor of five. The Ca2+ channel blocker, Mn2+ (0.5 mM), decreased slow-wave amplitude and the associated phasic contractions. These data agree with a previous study (12), suggesting that an oscillation in intracellular Ca2+ occurs during each slow-wave cycle. The present study suggests that the increase in intracellular Ca2+ during the slow wave is sufficient to activate the contractile apparatus.

1975 ◽  
Vol 229 (2) ◽  
pp. 484-488 ◽  
Author(s):  
AK Mukhopadhyay ◽  
LR Johnson ◽  
EM Copeland ◽  
NW Weisbrodt

The effect of intravenously administered secretin (0.5, 2.0, 6.0 U/kg-h) and intraduodenal acidification (13.2 meq/h HCl) on the electrical activity of the small bowel of three conscious dogs with gastric and duodenal cannulas was observed. Electrical activity was recorded in fasted as well as fed conditions through silver wire electrodes implanted along the entire length of the small bowel. Intravenous infusion of secretin in all dosages and in all dogs delayed the onset of the interdigestive myoelectric complex and reduced the total percentage of slow waves with superimposed spike potentials. Intraduodenal acidification also inhibited the interdigestive myoelectric complex, which developed incompletely with fewer action potentials on slow waves. Secretin did not produce any alteration in the fed pattern of activity, slow-wave frequency, or the caudal migration of the interdigestive myoelectric complex. The present study indicates that the nuerohumoral mechanisms responsible for initiation of the interdigestive myoelectric complex may be different from those responsible for its caudal migration.


2001 ◽  
Vol 280 (3) ◽  
pp. G491-G500 ◽  
Author(s):  
Graeme Donnelly ◽  
Timothy D. Jackson ◽  
Krista Ambrous ◽  
Jing Ye ◽  
Adeel Safdar ◽  
...  

In an in vitro model for distention-induced peristalsis in the guinea pig small intestine, the electrical activity, intraluminal pressure, and outflow of contents were studied simultaneously to search for evidence of myogenic control activity. Intraluminal distention induced periods of nifedipine-sensitive slow wave activity with superimposed action potentials, alternating with periods of quiescence. Slow waves and associated high intraluminal pressure transients propagated aborally, causing outflow of content. In the proximal small intestine, a frequency gradient of distention-induced slow waves was observed, with a frequency of 19 cycles/min in the first 1 cm and 11 cycles/min 10 cm distally. Intracellular recording revealed that the guinea pig small intestinal musculature, in response to carbachol, generated slow waves with superimposed action potentials, both sensitive to nifedipine. These slow waves also exhibited a frequency gradient. In addition, distention and cholinergic stimulation induced high-frequency membrane potential oscillations (∼55 cycles/min) that were not associated with distention-induced peristalsis. Continuous distention produced excitation of the musculature, in part neurally mediated, that resulted in periodic occurrence of bursts of distally propagating nifedipine-sensitive slow waves with superimposed action potentials associated with propagating intraluminal pressure waves that caused pulsatile outflow of content at the slow wave frequency.


1999 ◽  
Vol 77 (8) ◽  
pp. 598-605 ◽  
Author(s):  
Rosa Espinosa-Luna ◽  
Stephen M Collins ◽  
Luis M Montaño ◽  
Carlos Barajas-López

Intracellular recordings were obtained to investigate whether slow wave and spike type action potentials are present in cell cultures of the muscularis externa from the guinea pig small intestine. The muscularis externa of the small intestine was dissociated by using specific purified enzymes and gentle mechanical dissociation. Cells were plated on cover slips and maintained in culture for up to 4 weeks. Dissociated cells obtained in this way reorganized themselves in a few days to form small cell clumps showing spontaneous movements. Intracellular recordings of these clumps displayed both spike and slow wave type action potentials. Spikes were observed on top of some slow waves and were abolished by the addition of nifedipine or the removal of extracellular calcium. Slow waves, however, were nifedipine insensitive and temperature sensitive, and were abolished by octanol (a gap junction blocker) and forskolin (an adenyl cyclase activator). Slow waves were never observed in small clumps (<50 µm), suggesting that a critical mass of cells might be required for their generation. These observations demonstrated for the first time the presence of nifedipine-insensitive slow waves in cell cultures of the muscularis externa from the guinea pig small intestine. Cell cultures allow rigorous control of the immediate environment for the cells and this should facilitate future studies on the molecular and cellular mechanisms responsible for the slow waves in the gastrointestinal tract.Key words: smooth muscle, slow waves, spiking activity, gastrointestinal tract, gut, small intestine, electrophysiology, pacemaker activity, guinea pig.


1960 ◽  
Vol 38 (7) ◽  
pp. 777-801 ◽  
Author(s):  
E. E. Daniel ◽  
B. T. Wachter ◽  
A. J. Honour ◽  
A. Bogoch

Electrical activity of the small intestine of man and of dogs has been studied using monopolar recording techniques and spread of electrical activity in the small intestine of the dog using a bipolar recording technique. Motility was studied simultaneously. Electrical activity consisted of slow waves and action potentials which occurred when contractions were present. Action potentials were not conducted but slow waves sometimes spread aborally for short distances. Particular attention was paid to the relation of slow waves to action potentials and to motility. No consistent alteration in the frequency or configuration of slow waves was found associated with the occurrence of action potentials and motility, although serotonin or epinephrine altered slow wave frequency slightly. Slow waves usually were increased in amplitude during periods when motility and action potentials were occurring (during eating or balloon propulsion; after the administration of serotonin, neostigmine, physostigmine, or morphine). Slow wave amplitudes usually were diminished when motility was inhibited (by balloon distention; after administration of epinephrine, etc.). Action potentials tended to occur in phase with the slow waves, when the muscle electrode was positive relative to the indifferent electrode, but this was not always so during nonpropulsive contractions. There was also a correlation between the occurrence of distal spread of slow waves over the duodenum and upper jejunum and the ability of the intestine in this region to respond to balloon distention by propulsion.In the dog, body temperature consistently affected slow waves. A decrease of 10 °C diminished their frequencies to less than one-half and diminished their amplitude. Slow waves occurred at similar frequencies and with regular conduction after large doses of nicotine or atropine. Dibenzyline, dichloroisopropyl-norepinephrine, and vagotomy did not markedly alter slow wave frequencies. These findings and those in our studies with microelectrodes indicate that the slow waves are myogenic in origin, and represent electrical currents in the extracellular fluid initiated by periodic depolarizations of muscle cells of the small intestine.


1995 ◽  
Vol 73 (10) ◽  
pp. 1502-1511 ◽  
Author(s):  
John Malysz ◽  
David Richardsons ◽  
Laura Farraway ◽  
Jan D. Huizinga ◽  
Marie-Odile Christen

Intrinsic electrical activities in various isolated segments of the mouse small intestine were recorded (i) to characterize action potential generation and (ii) to obtain a profile on the ion channels involved in initiating the slow wave type action potentials (slow waves). Gradients in slow wave frequency, resting membrane potential, and occurrence of spiking activity were found, with the proximal intestine exhibiting the highest frequency, the most hyperpolarized cell membrane, and the greatest occurrence of spikes. The slow waves were only partially sensitive to L-type calcium channel blockers. Nifedipine, verapamil, and pinaverium bromide abolished spikes that occurred on the plateau phase of the slow waves in all tissues. The activity that remained in the presence of L-type calcium channel blockers, the upstroke potential, retained a similar amplitude to the original slow wave and was of identical frequency. The upstroke potential was not sensitive to a reduction in extracellular chloride or to the sodium channel blockers tetrodotoxin and mexiletine. Abolishment of the Na+ gradient by removal of 120 mM extracellular Na+ reduced the upstroke potential frequency by 13–18% and its amplitude by 50–70% in the ileum. The amplitude was similarly reduced by Ni2+ (up to 5 mM), and by flufenamic acid (100 μM), a nonspecific cation and chloride channel blocker. Gadolinium, a nonspecific blocker of cation and stretch-activated channels, had no effect. Throughout these pharmacological manipulations, a robust oscillation remained at 5–10 mV. This oscillation likely reflects pacemaker activity. It was rapidly abolished by removal of extracellular calcium but not affected by L-type calcium channel blockers. In summary, the mouse small intestine has been established as a model for research into slow wave generation and electrical pacemaker activity. The upstroke part of the slow wave has two components, the pacemaker component involves a non-L-type calcium channel.Key words: slow wave, pacemaker, calcium channel, pinaverium, smooth muscle.


1960 ◽  
Vol 38 (1) ◽  
pp. 777-801 ◽  
Author(s):  
E. E. Daniel ◽  
B. T. Wachter ◽  
A. J. Honour ◽  
A. Bogoch

Electrical activity of the small intestine of man and of dogs has been studied using monopolar recording techniques and spread of electrical activity in the small intestine of the dog using a bipolar recording technique. Motility was studied simultaneously. Electrical activity consisted of slow waves and action potentials which occurred when contractions were present. Action potentials were not conducted but slow waves sometimes spread aborally for short distances. Particular attention was paid to the relation of slow waves to action potentials and to motility. No consistent alteration in the frequency or configuration of slow waves was found associated with the occurrence of action potentials and motility, although serotonin or epinephrine altered slow wave frequency slightly. Slow waves usually were increased in amplitude during periods when motility and action potentials were occurring (during eating or balloon propulsion; after the administration of serotonin, neostigmine, physostigmine, or morphine). Slow wave amplitudes usually were diminished when motility was inhibited (by balloon distention; after administration of epinephrine, etc.). Action potentials tended to occur in phase with the slow waves, when the muscle electrode was positive relative to the indifferent electrode, but this was not always so during nonpropulsive contractions. There was also a correlation between the occurrence of distal spread of slow waves over the duodenum and upper jejunum and the ability of the intestine in this region to respond to balloon distention by propulsion.In the dog, body temperature consistently affected slow waves. A decrease of 10 °C diminished their frequencies to less than one-half and diminished their amplitude. Slow waves occurred at similar frequencies and with regular conduction after large doses of nicotine or atropine. Dibenzyline, dichloroisopropyl-norepinephrine, and vagotomy did not markedly alter slow wave frequencies. These findings and those in our studies with microelectrodes indicate that the slow waves are myogenic in origin, and represent electrical currents in the extracellular fluid initiated by periodic depolarizations of muscle cells of the small intestine.


2007 ◽  
Vol 292 (4) ◽  
pp. G1162-G1172 ◽  
Author(s):  
R. M. Gwynne ◽  
J. C. Bornstein

Mechanisms underlying nutrient-induced segmentation within the gut are not well understood. We have shown that decanoic acid and some amino acids induce neurally dependent segmentation in guinea pig small intestine in vitro. This study examined the neural mechanisms underlying segmentation in the circular muscle and whether the timing of segmentation contractions also depends on slow waves. Decanoic acid (1 mM) was infused into the lumen of guinea pig duodenum and jejunum. Video imaging was used to monitor intestinal diameter as a function of both longitudinal position and time. Circular muscle electrical activity was recorded by using suction electrodes. Recordings from sites of segmenting contractions showed they are always associated with excitatory junction potentials leading to action potentials. Recordings from sites oral and anal to segmenting contractions revealed inhibitory junction potentials that were time locked to those contractions. Slow waves were never observed underlying segmenting contractions. In paralyzed preparations, intracellular recording revealed that slow-wave frequency was highly consistent at 19.5 (SD 1.4) cycles per minute (c/min) in duodenum and 16.6 (SD 1.1) c/min in jejunum. By contrast, the frequencies of segmenting contractions varied widely (duodenum: 3.6–28.8 c/min, median 10.8 c/min; jejunum: 3.0–27.0 c/min, median 7.8 c/min) and sometimes exceeded slow-wave frequencies for that region. Thus nutrient-induced segmentation contractions in guinea pig small intestine do not depend on slow-wave activity. Rather they result from a neural circuit producing rhythmic localized activity in excitatory motor neurons, while simultaneously activating surrounding inhibitory motor neurons.


2017 ◽  
Vol 312 (3) ◽  
pp. G228-G245 ◽  
Author(s):  
John Malysz ◽  
Simon J. Gibbons ◽  
Siva A. Saravanaperumal ◽  
Peng Du ◽  
Seth T. Eisenman ◽  
...  

Myenteric plexus interstitial cells of Cajal (ICC-MY) in the small intestine are Kit+ electrical pacemakers that express the Ano1/TMEM16A Ca2+-activated Cl– channel, whose functions in the gastrointestinal tract remain incompletely understood. In this study, an inducible Cre-LoxP-based approach was used to advance the understanding of Ano1 in ICC-MY of adult mouse small intestine. KitCreERT2/+;Ano1Fl/Fl mice were treated with tamoxifen or vehicle, and small intestines (mucosa free) were examined. Quantitative RT-PCR demonstrated ~50% reduction in Ano1 mRNA in intestines of conditional knockouts (cKOs) compared with vehicle-treated controls. Whole mount immunohistochemistry showed a mosaic/patchy pattern loss of Ano1 protein in ICC networks. Ca2+ transients in ICC-MY network of cKOs displayed reduced duration compared with highly synchronized controls and showed synchronized and desynchronized profiles. When matched, the rank order for Ano1 expression in Ca2+ signal imaged fields of view was as follows: vehicle controls>>>cKO(synchronized)>cKO(desynchronized). Maintenance of Ca2+ transients’ synchronicity despite high loss of Ano1 indicates a large functional reserve of Ano1 in the ICC-MY network. Slow waves in cKOs displayed reduced duration and increased inter-slow-wave interval and occurred in regular- and irregular-amplitude oscillating patterns. The latter activity suggested ongoing interaction by independent interacting oscillators. Lack of slow waves and depolarization, previously reported for neonatal constitutive knockouts, were also seen. In summary, Ano1 in adults regulates gastrointestinal function by determining Ca2+ transients and electrical activity depending on the level of Ano1 expression. Partial Ano1 loss results in Ca2+ transients and slow waves displaying reduced duration, while complete and widespread absence of Ano1 in ICC-MY causes lack of slow wave and desynchronized Ca2+ transients. NEW & NOTEWORTHY The Ca2+-activated Cl− channel, Ano1, in interstitial cells of Cajal (ICC) is necessary for normal gastrointestinal motility. We knocked out Ano1 to varying degrees in ICC of adult mice. Partial knockout of Ano1 shortened the widths of electrical slow waves and Ca2+ transients in myenteric ICC but Ca2+ transient synchronicity was preserved. Near-complete knockout was necessary for transient desynchronization and loss of slow waves, indicating a large functional reserve of Ano1 in ICC. View this article's corresponding video summary at https://youtu.be/cyPtDP0KLY4 .


1993 ◽  
Vol 265 (4) ◽  
pp. G619-G627
Author(s):  
W. C. De Vos

This study characterizes the migrating spike complex (MSC) in the small intestine of the awake fasting cat and compares the MSC with interdigestive activity in the small intestine of other species. Electrical activity in each of 12 cats with implanted electrodes showed MSCs, bands of spike potentials which attenuated slow-wave frequency and amplitude as the MSCs progressed distally. MSCs occurred at variable frequency with intervals ranging from < 1 min to > 5 h and averaged 51.2 +/- 2.8 (SE) min. MSCs migrated at 1-8 mm/s, accelerating distally; the duration decreased distally such that the length of the bowel in a burst (2-3 cm proximally) was conserved. The MSC was associated with an intense prolonged contraction of duration similar to that of the MSC. Sometimes the MSCs occurred in close association, and when an MSC period was < 5.7 min, the second MSC propagated at a slower rate than the first. Frequently, a brief series of slow wave-associated spikes preceded an MSC. MSCs were not associated with slow waves. The MSC differs in several respects from the migrating myoelectric complex of other laboratory animals and is more appropriately classified in a category that includes giant migrating spikes, prolonged propagated contractions, power contractions, and migrating action potential complexes.


1961 ◽  
Vol 201 (1) ◽  
pp. 203-208 ◽  
Author(s):  
Alex Bortoff

The various configurations of externally recorded slow waves from the small intestine of the cat are compared to those recorded intracellularly. It is shown that the slow waves represent periodic depolarizations of longitudinal muscle cells and that the flow of current associated with these depolarizations is similar to that in a core conductor. By recording monopolarly from a segment of intestine immersed in a volume conductor, slow waves are obtained having configurations ranging from those approximating the true time course and polarity of the intracellular slow wave to those approximating its second time derivative. This is shown to be a function of the pressure exerted by the electrode on the tissue. From a consideration of these results, plus those recently obtained by others, it is suggested that both "propagation" and synchronization of slow waves are manifestations of a modulation of slow wave discharge brought about either by electrotonic spread of current via low resistance intercellular pathways, or by voltage field effects.


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