Regulation of slow wave frequency by IP3-sensitive calcium release in the murine small intestine

2001 ◽  
Vol 280 (3) ◽  
pp. G439-G448 ◽  
Author(s):  
John Malysz ◽  
Graeme Donnelly ◽  
Jan D. Huizinga
Keyword(s):  
Small Intestine ◽  
Slow Wave ◽  
Calcium Release ◽  
Cyclopiazonic Acid ◽  
Slow Waves ◽  
Wave Frequency ◽  
Propagation Characteristics ◽  
Intracellular Ca ◽  
Stimulation Of

Slow waves determine frequency and propagation characteristics of contractions in the small intestine, yet little is known about mechanisms of slow wave regulation. We propose a role for intracellular Ca2+, inositol 1,4,5,-trisphosphate (IP3)-sensitive Ca2+ release, and sarcoplasmic reticulum (SR) Ca2+ content in the regulation of slow wave frequency because 1) 1,2-bis(2-aminophenoxy)ethane- N,N,N′,N′-tetraacetic acid-AM, a cytosolic Ca2+ chelator, reduced the frequency or abolished the slow waves; 2) thapsigargin and cyclopiazonic acid (CPA), inhibitors of SR Ca2+-ATPase, decreased slow wave frequency; 3) xestospongin C, a reversible, membrane-permeable blocker of IP3-induced Ca2+release, abolished slow wave activity; 4) caffeine and phospholipase C inhibitors (U-73122, neomycin, and 2-nitro-4-carboxyphenyl- N, N-diphenylcarbamate) inhibited slow wave frequency; 5) in the presence of CPA or thapsigargin, stimulation of IP3 synthesis with carbachol, norepinephrine, or phenylephrine acting on α1-adrenoceptors initially increased slow wave frequency but thereafter increased the rate of frequency decline, 6) thimerosal, a sensitizing agent of IP3 receptors increased slow wave frequency, and 7) ryanodine, a selective modulator of Ca2+-induced Ca2+ release, had no effect on slow wave frequency. In summary, these data are consistent with a role of IP3-sensitive Ca2+ release and the rate of SR Ca2+ refilling in regulation of intestinal slow wave frequency.

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.

Migrating spike complex in the small intestine of the fasting cat

1993 ◽  
Vol 265 (4) ◽  
pp. G619-G627
Author(s):  
W. C. De Vos
Keyword(s):  
Small Intestine ◽  
Action Potential ◽  
Electrical Activity ◽  
Slow Wave ◽  
Close Association ◽  
Slow Waves ◽  
Wave Frequency ◽  
Laboratory Animals ◽  
Variable Frequency ◽  
Implanted Electrodes

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.

scholarly journals Electrical slow waves in the mouse oviduct are dependent on extracellular and intracellular calcium sources

2011 ◽  
Vol 301 (6) ◽  
pp. C1458-C1469 ◽  
Author(s):  
Rose Ellen Dixon ◽  
Fiona C. Britton ◽  
Salah A. Baker ◽  
Grant W. Hennig ◽  
Christina M. Rollings ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Slow Wave ◽  
Cyclopiazonic Acid ◽  
Wave Generation ◽  
Slow Waves ◽  
Resting Membrane Potential ◽  
Pacemaker Activity ◽  
Similar Frequency ◽  
Intracellular Ca ◽  
Serca Pump

Spontaneous contractions of the myosalpinx are critical for oocyte transport along the oviduct. Slow waves, the electrical events that underlie myosalpinx contractions, are generated by a specialized network of pacemaker cells called oviduct interstitial cells of Cajal (ICC-OVI). The ionic basis of oviduct pacemaker activity is unknown. Intracellular recordings and Ca2+ imaging were performed to examine the role of extracellular and intracellular Ca2+ sources in slow wave generation. RT-PCR was performed to determine the transcriptional expression of Ca2+ channels. Molecular studies revealed most isoforms of L- and T-type calcium channels (Cav1.2,1.3,1.4,3.1,3.2,3.3) were expressed in myosalpinx. Reduction of extracellular Ca2+ concentration ([Ca2+]o) resulted in the abolition of slow waves and myosalpinx contractions without significantly affecting resting membrane potential (RMP). Spontaneous Ca2+ waves spread through ICC-OVI cells at a similar frequency to slow waves and were inhibited by reduced [Ca2+]o. Nifedipine depolarized RMP and inhibited slow waves; however, pacemaker activity returned when the membrane was repolarized with reduced extracellular K+ concentration ([K+]o). Ni2+ also depolarized RMP but failed to block slow waves. The importance of ryanodine and inositol 1,4,5 trisphosphate-sensitive stores were examined using ryanodine, tetracaine, caffeine, and 2-aminoethyl diphenylborinate. Results suggest that although both stores are involved in regulation of slow wave frequency, neither are exclusively essential. The sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) pump inhibitor cyclopiazonic acid inhibited pacemaker activity and Ca2+ waves suggesting that a functional SERCA pump is necessary for pacemaker activity. In conclusion, results from this study suggest that slow wave generation in the oviduct is voltage dependent, occurs in a membrane potential window, and is dependent on extracellular calcium and functional SERCA pumps.

Differential modulation of caffeine- and IP3-induced calcium release in cultured arterial tissue

1999 ◽  
Vol 276 (5) ◽  
pp. C1115-C1120 ◽  
Author(s):  
Karl Dreja ◽  
Per Hellstrand
Keyword(s):  
Calcium Release ◽  
Cyclopiazonic Acid ◽  
Differential Modulation ◽  
Transient Responses ◽  
Inositol 1,4,5 Trisphosphate ◽  
Arterial Tissue ◽  
Intracellular Ca ◽  
Rat Tail

To investigate the Ca2+-dependent plasticity of sarcoplasmic reticulum (SR) function in vascular smooth muscle, transient responses to agents releasing intracellular Ca2+ by either ryanodine (caffeine) ord- myo-inositol 1,4,5-trisphosphate [IP3; produced in response to norepinephrine (NE), 5-hydroxytryptamine (5-HT), arginine vasopressin (AVP)] receptors in rat tail arterial rings were evaluated after 4 days of organ culture. Force transients induced by all agents were increased compared with those induced in fresh rings. Stimulation by 10% FCS during culture further potentiated the force and Ca2+ responses to caffeine (20 mM) but not to NE (10 μM), 5-HT (10 μM), or AVP (0.1 μM). The effect was persistent, and SR capacity was not altered after reversible depletion of stores with cyclopiazonic acid. The effects of serum could be mimicked by culture in depolarizing medium (30 mM K+) and blocked by the addition of verapamil (1 μM) or EGTA (1 mM) to the medium, lowering intracellular Ca2+ concentration ([Ca2+]i) during culture. These results show that modulation of SR function can occur in vitro by a mechanism dependent on long-term levels of basal [Ca2+]iand involving ryanodine- but not IP3 receptor-mediated Ca2+release.

Effect of cromakalim and lemakalim on slow waves and membrane currents in colonic smooth muscle

1991 ◽  
Vol 260 (2) ◽  
pp. C375-C382 ◽  
Author(s):  
J. M. Post ◽  
R. J. Stevens ◽  
K. M. Sanders ◽  
J. R. Hume
Keyword(s):  
Smooth Muscle ◽  
Membrane Potential ◽  
Slow Wave ◽  
Outward Current ◽  
Wave Activity ◽  
Slow Waves ◽  
Slow Wave Activity ◽  
Ca Current ◽  
K Current ◽  
Stimulation Of

The effects of cromakalim (BRL 34915) and its optical isomer lemakalim (BRL 38227) were investigated in intact tissue and freshly dispersed circular muscle cells from canine proximal colon. Cromakalim and lemakalim hyperpolarized resting membrane potential, shortened the duration of slow waves by abolishing the plateau phase, and decreased the frequency of slow waves. Glyburide, a K channel blocker, prevented the effect of cromakalim on slow-wave activity. The mechanisms of these alterations in slow-wave activity were studied in isolated myocytes under voltage-clamp conditions. Cromakalim and lemakalim increased the magnitude of a time-independent outward K current, but cromakalim also reduced the peak outward K current. Glyburide inhibited lemakalim stimulation of the time-independent background current. Nisoldipine also reduced the peak outward current, and in the presence of nisoldipine, cromakalim did not affect the peak outward component of current. This suggested that cromakalim may block a Ca-dependent component of the outward current. Lemakalim did not affect the peak outward current. We tested whether the effects of cromakalim on outward current might be indirect due to an effect on inward Ca current. Cromakalim, but not lemakalim, was found to inhibit L-type Ca channels; however, glyburide did not alter cromakalim inhibition of inward Ca current. We conclude that the effects of cromakalim and lemakalim on membrane potential and slow waves in colonic smooth muscle appear to result primarily from stimulation of a time-independent background K conductance. The effects of these compounds on channel activity may explain the inhibitory effect of these compounds on contractile activity.

scholarly journals Prostaglandin regulation of gastric slow waves and peristalsis

2009 ◽  
Vol 296 (6) ◽  
pp. G1180-G1190 ◽  
Author(s):  
Abigail S. Forrest ◽  
Grant W. Hennig ◽  
Sari Jokela-Willis ◽  
Chong Doo Park ◽  
Kenton M. Sanders
Keyword(s):  
Slow Wave ◽  
Slow Waves ◽  
Wave Frequency ◽  
Functional Coupling ◽  
Receptor Agonists ◽  
Gastric Corpus ◽  
Gastric Peristalsis ◽  
Chronotropic Effects ◽  
Cells Of Cajal ◽  
The Impact

Gastric emptying depends on functional coupling of slow waves between the corpus and antrum, to allow slow waves initiated in the gastric corpus to propagate to the pyloric sphincter and generate gastric peristalsis. Functional coupling depends on a frequency gradient where slow waves are generated at higher frequency in the corpus and drive the activity of distal pacemakers. Simultaneous intracellular recording from corpus and antrum was used to characterize the effects of PGE2 on slow waves in the murine stomach. PGE2 increased slow-wave frequency, and this effect was mimicked by EP3, but not by EP2, receptor agonists. Chronotropic effects were due to EP3 receptors expressed by intramuscular interstitial cells of Cajal because these effects were not observed in W/W V mice. Although the integrated chronotropic effects of EP3 receptor agonists were deduced from electrophysiological experiments, no clear evidence of functional uncoupling was observed with two-point electrical recording. Gastric peristalsis was also monitored by video imaging and spatiotemporal maps to study the impact of chronotropic agonists on propagating contractions. EP3 receptor agonists increased the frequency of peristaltic contractions and caused ectopic sites of origin and collisions of peristaltic waves. The impact of selective regional application of chronotropic agonists was investigated by use of a partitioned bath. Antral slow waves followed enhanced frequencies induced by stimulation of the corpus, and corpus slow waves followed when slow-wave frequency was elevated in the antrum. This demonstrated reversal of slow-wave propagation with selective antral chronotropic stimulation. These studies demonstrate the impact of chronotropic agonists on regional intrinsic pacemaker frequency and integrated gastric peristalsis.

Voltage sensitivity of slow wave frequency in isolated circular muscle strips from guinea pig gastric antrum

1999 ◽  
Vol 276 (2) ◽  
pp. G518-G528 ◽  
Author(s):  
S.-M. Huang ◽  
S. Nakayama ◽  
S. Iino ◽  
T. Tomita
Keyword(s):  
Smooth Muscle ◽  
Guinea Pig ◽  
Slow Wave ◽  
Circular Muscle ◽  
Gastric Antrum ◽  
Slow Waves ◽  
Wave Frequency ◽  
Voltage Sensitivity ◽  
Dependent Manner ◽  
Circular Smooth Muscle

In circular muscle preparations isolated from the guinea pig gastric antrum, regular spontaneous electrical activity (slow waves) was recorded. Under normal conditions (6 mM K+), the frequency and shape of the slow waves were similar to those observed in ordinary stomach smooth muscle preparations. When the resting membrane potential was hyperpolarized and depolarized by changing the extracellular K+ concentration (2–18 mM), the frequency of slow waves decreased and increased, respectively. Application of cromakalim hyperpolarized the cell membrane and reduced the frequency of slow waves in a dose-dependent manner. Cromakalim (3 μM) hyperpolarized the membrane, and slow waves ceased in most preparations. In the presence of cromakalim, subsequent increases in the extracellular K+ concentration restored the frequency of slow waves accompanied by depolarization. Also, glibenclamide completely antagonized this effect of cromakalim. In smooth muscle strips containing both circular and longitudinal muscle layers, such changes in the slow wave frequency were not observed. It was concluded that the maneuver of isolating circular smooth muscle altered the voltage dependence of the slow wave frequency.

Effect of food intake on intestinal cholesterol synthesis in rats

1986 ◽  
Vol 251 (3) ◽  
pp. G362-G369
Author(s):  
K. R. Feingold ◽  
G. Zsigmond ◽  
S. R. Lear ◽  
A. H. Moser
Keyword(s):  
Small Intestine ◽  
Food Intake ◽  
Direct Contact ◽  
Cholesterol Synthesis ◽  
Third Trimester ◽  
Increase Food Intake ◽  
Effect Of Food ◽  
Small Intestinal ◽  
Stimulation Of

The mechanism by which diabetes results in an increase in small intestinal cholesterol synthesis is unknown. Previous studies have demonstrated that limiting food intake prevents the increase in intestinal cholesterol synthesis, and it has therefore been proposed that the stimulation of cholesterol synthesis in the small intestine is secondary to the hyperphagia that is associated with poorly controlled diabetes. To shed further light on the role of hyperphagia we have studied the effect on cholesterol synthesis of a variety of conditions that increase food intake. In third-trimester pregnant animals, lactating animals, obese animals, and in animals infused intragastrically with 16 g glucose/day vs. 8 g glucose/day, we have observed that an increase in food intake is associated with an increase in small intestinal cholesterol synthesis. Furthermore, these findings support the hypothesis that hyperphagia is the chief stimulus for the increase in cholesterol synthesis in the small intestine of diabetic animals. Additional studies have demonstrated that simply increasing the bulk of food ingested by adding Alphacel to the diet does not alter cholesterol synthesis in the small intestine. Lastly, in animals in whom Thiry fistulas were surgically constructed we observed that cholesterol synthesis is increased in the diabetic animals in both the segment of the small intestine in contact with the food stream and the segment of the small intestine that is excluded from contact. This observation suggests that the direct contact of the intestinal mucosa with caloric sources is not the sole trigger for increasing small intestinal cholesterol synthesis in hyperphagic diabetic animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Ryanodine-Sensitive Stores Regulate the Excitability of AH Neurons in the Myenteric Plexus of Guinea-Pig Ileum

2000 ◽  
Vol 84 (6) ◽  
pp. 2777-2785 ◽  
Author(s):  
K. Hillsley ◽  
J. L. Kenyon ◽  
T. K. Smith
Keyword(s):  
Sensory Processing ◽  
Calcium Release ◽  
Excitatory Postsynaptic Potential ◽  
Similar Time ◽  
Intracellular Ca ◽  
Time Courses ◽  
High Concentrations ◽  
Calcium Induced Calcium Release ◽  
Activity Dependent

Myenteric afterhyperpolarizing (AH) neurons are primary afferent neurons within the gastrointestinal tract. Stimulation of the intestinal mucosa evokes action potentials (AP) that are followed by a slow afterhyperpolarization (AHPslow) in the soma. The role of intracellular Ca2+ ([Ca2+]i) and ryanodine-sensitive Ca2+ stores in modulating the electrical activity of myenteric AH neurons was investigated by recording membrane potential and bis-fura-2 fluorescence from 34 AH neurons. Mean resting [Ca2+]i was ∼200 nM. Depolarizing current pulses that elicited APs evoked AHPslow and an increase in [Ca2+]i, with similar time courses. The amplitudes and durations of AHPslow and the Ca2+ transient were proportional to the number of evoked APs, with each AP increasing [Ca2+]i by ∼50 nM. Ryanodine (10 μM) significantly reduced both the amplitude and duration (by 60%) of the evoked Ca2+ transient and AHPslow over the range of APs tested (1–15). Calcium-induced calcium release (CICR) was graded and proportional to the number of APs, with each AP triggering a rise in [Ca2+]i of ∼30 nM Ca2+ via CICR. This indicates that CICR amplifies Ca2+ influx. Similar changes in [Ca2+]i and AHPslow were evoked by two APs in control and six APs in ryanodine. Thus, the magnitude of the change in bulk [Ca2+]i and not the source of the Ca2+ is the determinant of the magnitude of AHPslow. Furthermore, lowering of free [Ca2+]i, either by reducing extracellular Ca2+ or injecting high concentrations of Ca2+buffer, induced depolarization, increased excitability, and abolition of AHPslow. In addition, activation of synaptic input to AH neurons elicited a slow excitatory postsynaptic potential (sEPSP) that was completely blocked in ryanodine. These results demonstrate the importance of [Ca2+]i and CICR in sensory processing in AH neurons. Activity-dependent CICR may be a mechanism to grade the output of AH neurons according to the intensity of sensory input.

Quantitative cellular description of gastric slow wave activity

2008 ◽  
Vol 294 (4) ◽  
pp. G989-G995 ◽  
Author(s):  
Alberto Corrias ◽  
Martin L. Buist
Keyword(s):  
Slow Wave ◽  
Interstitial Cells Of Cajal ◽  
Quantitative Description ◽  
Wave Activity ◽  
Slow Waves ◽  
Slow Wave Activity ◽  
Good Correspondence ◽  
Gastric Slow Wave ◽  
Intracellular Ca ◽  
Cells Of Cajal

Interstitial cells of Cajal (ICC) are responsible for the spontaneous and omnipresent electrical activity in the stomach. A quantitative description of the intracellular processes whose coordinated activity is believed to generate electrical slow waves has been developed and is presented here. In line with recent experimental evidence, the model describes how the interplay between the mitochondria and the endoplasmic reticulum in cycling intracellular Ca2+ provides the primary regulatory signal for the initiation of the slow wave. The major ion channels that have been identified as influencing slow wave activity have been modeled according to data obtained from isolated ICC. The model has been validated by comparing the simulated profile of the slow waves with experimental recordings and shows good correspondence in terms of frequency, amplitude, and shape in both control and pharmacologically altered conditions.

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