Generation of slow wave type action potentials in the mouse small intestine involves a non-L-type calcium channel

1995 ◽  
Vol 73 (10) ◽  
pp. 1502-1511 ◽  
Author(s):  
John Malysz ◽  
David Richardsons ◽  
Laura Farraway ◽  
Jan D. Huizinga ◽  
Marie-Odile Christen
Keyword(s):  
Small Intestine ◽  
Calcium Channel ◽  
Slow Wave ◽  
Calcium Channel Blockers ◽  
Action Potentials ◽  
Slow Waves ◽  
Pacemaker Activity ◽  
Channel Blockers ◽  
Wave Type ◽  
Mouse Small Intestine

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.

Effect of secretin on electrical activity of small intestine

1975 ◽  
Vol 229 (2) ◽  
pp. 484-488 ◽  
Author(s):  
AK Mukhopadhyay ◽  
LR Johnson ◽  
EM Copeland ◽  
NW Weisbrodt
Keyword(s):  
Small Intestine ◽  
Small Bowel ◽  
Electrical Activity ◽  
Slow Wave ◽  
Intravenous Infusion ◽  
Action Potentials ◽  
Slow Waves ◽  
Wave Frequency ◽  
Conscious Dogs ◽  
Total Percentage

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.

scholarly journals Conditional genetic deletion of Ano1 in interstitial cells of Cajal impairs Ca2+ transients and slow waves in adult mouse small intestine

2017 ◽  
Vol 312 (3) ◽  
pp. G228-G245 ◽  
Author(s):  
John Malysz ◽  
Simon J. Gibbons ◽  
Siva A. Saravanaperumal ◽  
Peng Du ◽  
Seth T. Eisenman ◽  
...  
Keyword(s):  
Small Intestine ◽  
Slow Wave ◽  
Interstitial Cells Of Cajal ◽  
Adult Mouse ◽  
Rank Order ◽  
Interstitial Cells ◽  
Slow Waves ◽  
Functional Reserve ◽  
Mouse Small Intestine ◽  
Cells Of Cajal

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 .

Effect of different calcium channel blockers on inhibitory junction potentials and slow waves in porcine ileum

Life Sciences ◽  
1997 ◽  
Vol 60 (12) ◽  
pp. 883-892 ◽  
Author(s):  
J.R. Borderies ◽  
E. Goñalons ◽  
F. Angel ◽  
P. Vergara ◽  
M. Jiménez
Keyword(s):  
Calcium Channel ◽  
Calcium Channel Blockers ◽  
Slow Waves ◽  
Channel Blockers

A mathematical model of pacemaker activity recorded from mouse small intestine

2006 ◽  
Vol 364 (1842) ◽  
pp. 1135-1154 ◽  
Author(s):  
Jae Boum Youm ◽  
Nari Kim ◽  
Jin Han ◽  
Euiyong Kim ◽  
Hyun Joo ◽  
...  
Keyword(s):  
Mathematical Model ◽  
Small Intestine ◽  
Action Potentials ◽  
Interstitial Cells Of Cajal ◽  
Animal Experiments ◽  
Pacemaker Activity ◽  
Mouse Small Intestine ◽  
Pacemaker Potentials ◽  
Cyclic Changes ◽  
Cells Of Cajal

The pacemaker activity of interstitial cells of Cajal (ICCs) has been known to initiate the propagation of slow waves along the whole gastrointestinal tract through spontaneous and repetitive generation of action potentials. We studied the mechanism of the pacemaker activity of ICCs in the mouse small intestine and tested it using a mathematical model. The model includes ion channels, exchanger, pumps and intracellular machinery for Ca 2+ regulation. The model also incorporates inositol 1,4,5-triphosphate (IP 3 ) production and IP 3 -mediated Ca 2+ release activities. Most of the parameters were obtained from the literature and were modified to fit the experimental results of ICCs from mouse small intestine. We were then able to compose a mathematical model that simulates the pacemaker activity of ICCs. The model generates pacemaker potentials regularly and repetitively as long as the simulation continues. The frequency was set at 20 min −1 and the duration at 50% repolarization was 639 ms. The resting and overshoot potentials were −78 and +1.2 mV, respectively. The reconstructed pacemaker potentials closely matched those obtained from animal experiments. The model supports the idea that cyclic changes in [Ca 2+ ] i and [IP 3 ] play key roles in the generation of ICC pacemaker activity in the mouse small intestine.

scholarly journals The myogenic component in distention-induced peristalsis in the guinea pig small intestine

2001 ◽  
Vol 280 (3) ◽  
pp. G491-G500 ◽  
Author(s):  
Graeme Donnelly ◽  
Timothy D. Jackson ◽  
Krista Ambrous ◽  
Jing Ye ◽  
Adeel Safdar ◽  
...  
Keyword(s):  
Small Intestine ◽  
Guinea Pig ◽  
Slow Wave ◽  
Action Potentials ◽  
Slow Waves ◽  
Intraluminal Pressure ◽  
Control Activity ◽  
Potential Oscillations ◽  
Frequency Gradient

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.

Slow wave and spike action potentials recorded in cell cultures from the muscularis externa of the guinea pig small intestine

1999 ◽  
Vol 77 (8) ◽  
pp. 598-605 ◽  
Author(s):  
Rosa Espinosa-Luna ◽  
Stephen M Collins ◽  
Luis M Montaño ◽  
Carlos Barajas-López
Keyword(s):  
Small Intestine ◽  
Guinea Pig ◽  
Cell Cultures ◽  
Slow Wave ◽  
Action Potentials ◽  
Critical Mass ◽  
Slow Waves ◽  
Intracellular Recordings ◽  
Spontaneous Movements ◽  
Muscularis Externa

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.

THE RELATIONSHIP BETWEEN ELECTRICAL AND MECHANICAL ACTIVITY OF THE SMALL INTESTINE OF DOG AND MAN

1960 ◽  
Vol 38 (7) ◽  
pp. 777-801 ◽  
Author(s):  
E. E. Daniel ◽  
B. T. Wachter ◽  
A. J. Honour ◽  
A. Bogoch
Keyword(s):  
Small Intestine ◽  
Electrical Activity ◽  
Slow Wave ◽  
Action Potentials ◽  
Extracellular Fluid ◽  
Slow Waves ◽  
Mechanical Activity ◽  
Electrical Currents ◽  
Bipolar Recording ◽  
Balloon Distention

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.

THE RELATIONSHIP BETWEEN ELECTRICAL AND MECHANICAL ACTIVITY OF THE SMALL INTESTINE OF DOG AND MAN

1960 ◽  
Vol 38 (1) ◽  
pp. 777-801 ◽  
Author(s):  
E. E. Daniel ◽  
B. T. Wachter ◽  
A. J. Honour ◽  
A. Bogoch
Keyword(s):  
Small Intestine ◽  
Electrical Activity ◽  
Slow Wave ◽  
Action Potentials ◽  
Extracellular Fluid ◽  
Slow Waves ◽  
Mechanical Activity ◽  
Electrical Currents ◽  
Bipolar Recording ◽  
Balloon Distention

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.

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