Control of colonic motility using electrical stimulation to modulate enteric neural activity

2021 ◽  
Author(s):  
Bradley Barth ◽  
Lee Travis ◽  
Nick J Spencer ◽  
Warren M. Grill
Keyword(s):  
Electrical Stimulation ◽  
Refractory Period ◽  
Colonic Motility ◽  
Gastrointestinal Transit ◽  
Absolute Refractory Period ◽  
Refractory Periods ◽  
Colonic Motor ◽  
The Mean ◽  
Insight Into

Electrical stimulation of the enteric nervous system (ENS) is an attractive approach to modify gastrointestinal transit. Colonic motor complexes (CMCs) occur with a periodic rhythm, but the ability to elicit a premature CMC depends, at least in part, upon the intrinsic refractory properties of the ENS, which are presently unknown. The objectives of this study were to record myoelectric complexes (MCs, the electrical correlates of CMCs) in the smooth muscle and (i) determine the refractory periods of MCs, (ii) inform and evaluate closed-loop stimulation to repetitively evoke MCs, and (iii) identify stimulation methods to suppress MC propagation. We dissected the colon from male and female C57BL/6 mice, preserving the integrity of intrinsic circuitry while removing the extrinsic nerves, and measured properties of spontaneous and evoked MCs in vitro. Hexamethonium abolished spontaneous and evoked MCs, confirming the necessary involvement of the ENS for electrically-evoked MCs. Electrical stimulation reduced the mean interval between evoked and spontaneous CMCs (24.6 ± 3.5 vs 70.6 ± 15.7 s, p = 0.0002, n = 7). The absolute refractory period was 4.3 s (95% CI = 2.8 - 5.7 s, R2 = 0.7315, n = 8). Electrical stimulation applied during fluid distention-evoked MCs led to an arrest of MC propagation, and following stimulation, MC propagation resumed at an increased velocity (n = 9). The timing parameters of electrical stimulation increased the rate of evoked MCs and the duration of entrainment of MCs, and the refractory period provides insight into timing considerations for designing neuromodulation strategies to treat colonic dysmotility.

Respiration-dependent Movements of the Column of Stylidium gvaminifolium

1981 ◽  
Vol 8 (1) ◽  
pp. 45 ◽  
Author(s):  
G.P Findlay ◽  
N Findlay
Keyword(s):  
Refractory Period ◽  
Angular Displacement ◽  
Metabolic Energy ◽  
Original Position ◽  
Firing Process ◽  
Mechanical Stimuli ◽  
Anaerobic Conditions ◽  
Absolute Refractory Period ◽  
Refractory Periods ◽  
Graded Responses

The column of the trigger plant, Stylidium graminifolium, when fully set responds to mechanical stimuli by flipping through an angle of about 4 radians in a fast firing movement lasting about 15-30 ms, and then slowly resetting to its original position in about 400 s. After resetting there is an absolute refractory period of about 500 s during which no further response to stimuli can be initiated, followed by a relative refractory period when graded responses increasing in rate and magnitude with time can be obtained. The resetting movement and the process, occurring during the refractory period, allowing subsequent firing to occur, are inhibited when the air surrounding the column is replaced by nitrogen. The firing movement, however, is not affected by these anaerobic conditions. Thus the firing movement is caused by passive physical forces, rapidly utilizing potential energy from a store built up during the previous resetting and refractory periods. Removal of the labellum, which the column touches when set, causes the column to oscillate with amplitude of about 3-3.5 radians and period of 1-2 ks. When the column is held at a constant angular displacement it develops an oscillatory torque with similar period. These oscillations are inhibited at all stages of the cycle by anaerobic conditions. It appears that the oscillatory behaviour is not a slowed-down firing process followed by normal resetting, but is linked throughout the cycle to the metabolic energy supply.

scholarly journals Microtubule minus-end stability is dictated by the tubulin off-rate

2019 ◽  
Vol 218 (9) ◽  
pp. 2841-2853 ◽  
Author(s):  
Claire Strothman ◽  
Veronica Farmer ◽  
Göker Arpağ ◽  
Nicole Rodgers ◽  
Marija Podolski ◽  
...  
Keyword(s):  
Dynamic Instability ◽  
In Vitro Reconstitution ◽  
Primary Determinant ◽  
Mean Size ◽  
The Mean ◽  
The Difference ◽  
Insight Into ◽  
Dynamic Organization ◽  
In Cells

Dynamic organization of microtubule minus ends is vital for the formation and maintenance of acentrosomal microtubule arrays. In vitro, both microtubule ends switch between phases of assembly and disassembly, a behavior called dynamic instability. Although minus ends grow slower, their lifetimes are similar to those of plus ends. The mechanisms underlying these distinct dynamics remain unknown. Here, we use an in vitro reconstitution approach to investigate minus-end dynamics. We find that minus-end lifetimes are not defined by the mean size of the protective GTP-tubulin cap. Rather, we conclude that the distinct tubulin off-rate is the primary determinant of the difference between plus- and minus-end dynamics. Further, our results show that the minus-end–directed kinesin-14 HSET/KIFC1 suppresses tubulin off-rate to specifically suppress minus-end catastrophe. HSET maintains its protective minus-end activity even when challenged by a known microtubule depolymerase, kinesin-13 MCAK. Our results provide novel insight into the mechanisms of minus-end dynamics, essential for our understanding of microtubule minus-end regulation in cells.

UNIT ACTIVITY IN THE PARAVENTRICULAR NUCLEUS OF FEMALE RATS AT DIFFERENT STAGES OF THE REPRODUCTIVE CYCLE AND AFTER OVARIECTOMY, WITH OR WITHOUT OESTROGEN OR PROGESTERONE TREATMENT

1973 ◽  
Vol 59 (3) ◽  
pp. 545-558 ◽  
Author(s):  
H. NEGORO ◽  
S. VISESSUWAN ◽  
R. C. HOLLAND
Keyword(s):  
Firing Rate ◽  
Paraventricular Nucleus ◽  
Reproductive Cycle ◽  
Refractory Period ◽  
Full Term ◽  
Ovariectomized Rats ◽  
Oestrogen Treatment ◽  
Absolute Refractory Period ◽  
Firing Rates ◽  
The Mean

SUMMARY Spontaneous firing rates were determined from extracellular recordings made from 878 antidromically identified units in the paraventricular nucleus (PVN) during the reproductive cycle of the female rat and in analytical experiments. In the latter, rats were ovariectomized and subsequently received either no treatment or oestrogen and/or progesterone. Among rats at metoestrus, dioestrus, mid-pregnancy and in ovariectomized progesterone-treated groups there was no significant difference in the firing rates. However, they were significantly lower than the rates recorded during pro-oestrus, oestrus, full-term pregnancy, the day of parturition, during lactation and in ovariectomized, oestrogen-treated rats. In spayed rats the mean firing rate was significantly lower than at pro-oestrus, oestrus, fullterm pregnancy, the 24 h period after parturition, during lactation and after oestrogen treatment. When progesterone was given subcutaneously to oestrogenized rats, the PVN activity, increased by oestrogen, was significantly depressed 4 h after administration. By 8 h the firing rate had completely recovered. The frequency distribution of the firing rates in pro-oestrus and oestrus showed an approximately normal distribution while those in metoestrus and dioestrus and mid-pregnancy had a Poisson distribution. At full term there were two peaks: one in the range of 3–5 spikes/s and the other less than one spike/s. The distribution was approximately normal on the day of parturition and subsequently the pattern became irregular. In ovariectomized rats and those treated with progesterone it was of a Poisson type while there was a distinct shift to higher frequencies after oestrogen treatment. The mean absolute refractory period, measured for each unit, varied and appears to be dependent on hormonal conditions. It was short in oestrus and long in dioestrus and mid-pregnancy. Oestrogen treatment significantly shortened the absolute refractory period of ovariectomized rats.

scholarly journals Morphologic changes in boar sperm nuclei with reduced disulfide bonds in electrostimulated porcine oocytes

Reproduction ◽  
2006 ◽  
Vol 131 (3) ◽  
pp. 603-611 ◽  
Author(s):  
Michiko Nakai ◽  
Naomi Kashiwazaki ◽  
Akiko Takizawa ◽  
Naoki Maedomari ◽  
Manabu Ozawa ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Blastocyst Stage ◽  
Blastocyst Formation ◽  
The Mean ◽  
Sperm Nuclei ◽  
Morphologic Changes ◽  
Number Of Cells ◽  
Stimulation Of ◽  
Nuclear Decondensation

In pigs, failure of sperm nuclear decondensation has been reported after injection into oocytes. We examined the effects of pretreating sperm heads with Triton X-100 (TX-100) and dithiothreitol (DTT) and of electrical stimulation of oocytes after sperm head injection on time-dependent morphologic changes in sperm nuclei andin vitrodevelopment to the blastocyst stage. In experiment 1, spermatozoa were pretreated with 1% TX-100 and 5 mM DTT (T + D) or not treated, and then injected intoin vitromatured oocytes. Electrical stimulation (1.5 kV/cm, 20 μs DC pulse) was applied to the oocytes 1 h after injection (stimulated group) or was not applied (unstimulated group). Some of the oocytes in each group were evaluated at hourly intervals until 10 h after injection for morphologic changes in the sperm nuclei. Unstimulated oocytes injected with untreated spermatozoa showed a delayed peak in the rate of nuclear decondensation (39.4–44.1%, 3–6 h after injection) compared with oocytes injected with T + D-treated spermatozoa (57.0% and 52.6%, 1 and 2 h, respectively). The rate of male pronucleus formation peaked 6 h after stimulation (by 40–60%) after injected oocytes had been stimulated with an electrical pulse, irrespective of whether or not the spermatozoa had been pretreated. In unstimulated oocytes, the rate of male pronucleus formation did not increase and stayed at the basal level (less than 20%) throughout the culture period, regardless of the sperm treatment. Thus, T + D treatment of spermatozoa did not affect completion of fertilization. In experiment 2, we evaluated the effects of electrical stimulation and sperm treatment with T + D on the rate of blastocyst formation and the mean number of cells per blastocyst. Oocytes stimulated after injection with either T + D-treated or untreated spermatozoa showed significantly higher percentages of blastocyst formation (24.8% and 27.1% respectively) than did unstimulated oocytes (1.1% and 4.1% for T + D-treated and untreated respectively;P< 0.01 by Duncan’s multiple-range test). The rate of blastocyst formation did not differ between the T + D-treated and untreated groups. The mean number of cells per blastocyst did not differ among any of the groups (14.0–29.4 cells). These results suggest that pretreatment of sperm with TX-100 and DTT shifted the timing of sperm nuclear decondensation forward. However, pronucleus formation and development to the blastocyst stagein vitrowere not improved by sperm treatment. Thus, electrical stimulation of injected oocytes enhancesin vitrodevelopment to the blastocyst stage in pigs.

Advances in colonic motor complexes in mice

2021 ◽  
Vol 320 (1) ◽  
pp. G12-G29
Author(s):  
N. J. Spencer ◽  
M. Costa ◽  
T. J. Hibberd ◽  
J. D. Wood
Keyword(s):  
Colonic Motility ◽  
Serotonin Release ◽  
Mechanical Stimuli ◽  
Gi Tract ◽  
Mouse Colon ◽  
Colonic Motor ◽  
Large Populations ◽  
Ec Cells ◽  
Gi Motility

The primary functions of the gastrointestinal (GI) tract are to absorb nutrients, water, and electrolytes that are essential for life. This is accompanied by the capability of the GI tract to mix ingested content to maximize absorption and effectively excrete waste material. There have been major advances in understanding intrinsic neural mechanisms involved in GI motility. This review highlights major advances over the past few decades in our understanding of colonic motor complexes (CMCs), the major intrinsic neural patterns that control GI motility. CMCs are generated by rhythmic coordinated firing of large populations of myenteric neurons. Initially, it was thought that serotonin release from the mucosa was required for CMC generation. However, careful experiments have now shown that neither the mucosa nor endogenous serotonin are required, although, evidence suggests enteroendocrine (EC) cells modulate CMCs. The frequency and extent of propagation of CMCs are highly dependent on mechanical stimuli (circumferential stretch). In summary, the isolated mouse colon emerges as a good model to investigate intrinsic mechanisms underlying colonic motility and provides an excellent preparation to explore potential therapeutic agents on colonic motility, in a highly controlled in vitro environment. In addition, during CMCs, the mouse colon facilitates investigations into the emergence of dynamic assemblies of extensive neural networks, applicable to the nervous system of different organisms.

Changes in colonic motility following abdominal irradiation in dogs

1993 ◽  
Vol 264 (6) ◽  
pp. G1024-G1030 ◽  
Author(s):  
R. W. Summers ◽  
B. Hayek
Keyword(s):  
Colonic Motility ◽  
Mean Amplitude ◽  
X Rays ◽  
Motor Patterns ◽  
Colonic Motor ◽  
Before And After ◽  
Irradiation Dosage ◽  
The Mean ◽  
Giant Migrating Contractions

The purpose of the study was to compare colonic motor patterns before and after a single abdominal dose of X-rays in dogs. Recordings were made from five serosally implanted strain gauges at equidistant intervals along the colon in seven dogs (2 dogs also had 2 jejunal electrodes and 1 had ileal electrodes). Control recordings were made for 3 h in the fasted state and daily for 2 wk after an absorbed X-ray dose of 938 cGy was delivered to the abdomen. The duration of migrating colonic motor complexes decreased from 7.2 +/- 0.5 to 3.9 +/- 0.4 min while the mean amplitude fell from 10.3 +/- 0.6 to 1.8 +/- 0.2 g (P < 0.05). The rate of nonmigrating colonic motor complex occurrence increased from 0.6 +/- 0.1 to 1.2 +/- 0.2 per hour (P < 0.05). Colonic giant migrating contractions were rarely observed during control recordings (2 in 80 h of recording). In contrast, repetitive clusters of giant contractions were observed 5-8 days after exposure in five of seven dogs (1.5/h) and were associated with restlessness, whining, and passage of diarrheal stools (sometimes bloody) with nearly every occurrence. The basic colonic motility patterns were less disrupted than were jejunal myoelectric patterns at the same irradiation dosage. However, the study demonstrates the important role of colonic giant migrating contractions in pathological diarrheal states such as irradiation injury.

scholarly journals Effects of Preharvest Methyl Jasmonate Elicitation and Electrical Stimulation on Camptothecin Production by In Vitro Plants of Ophiorrhiza ridleyana Craib

2021 ◽  
Vol 11 (10) ◽  
pp. 4555
Author(s):  
Supakit Pisitpaibool ◽  
Suchada Sukrong ◽  
Kijchai Kanjanaprapakul ◽  
Muenduen Phisalaphong
Keyword(s):  
Tissue Culture ◽  
Electrical Stimulation ◽  
Methyl Jasmonate ◽  
Culture Medium ◽  
Solid Culture ◽  
Direct Electric Current ◽  
Solid Culture Medium ◽  
The Mean ◽  
Stems And Leaves

To enhance plant camptothecin (CPT) production in vitro, 5-month-old Ophiorrhiza ridleyana Craib plant cultures were treated with solutions of methyl jasmonate (MeJA) dissolved in ethanol, which were applied to the surface of the solid culture medium. It was demonstrated that the maximum CPT content in the tissue-cultured plants was achieved after 12 h elicitation with 50 µM MeJA. The mean CPT contents in roots and stems were 50.8 and 67.0 µg/g DW, respectively, which were approximately 1.8- and 2.6-fold higher, respectively, than those of the control. However, MeJA elicitation showed no significant effect on CPT accumulation in O. ridleyana leaves. Moreover, it was found that direct electric current (DC) stimulation also significantly increased CPT accumulation in O. ridleyana. The treatment with DC at 20 mA for 3 min of stimulation enhanced 3-fold the CPT content in roots, stems, and leaves to 41.9, 36.0 and 19.6 µg/g DW, respectively, which were approximately 1.5-, 1.7- and 1.4-fold higher, respectively, as compared to those of the control. The results demonstrate that preharvest treatment by MeJA elicitation and electrical stimulation can be beneficial for secondary metabolite production of CPT in tissue-culture plants of O. ridleyana.

Minimal mass required for induction of a sustained arrhythmia in isolated atrial segments

1962 ◽  
Vol 202 (2) ◽  
pp. 232-236 ◽  
Author(s):  
Theodore C. West ◽  
Jorge F. Landa
Keyword(s):  
Electrical Stimulation ◽  
Left Atrium ◽  
Right Atrium ◽  
Refractory Period ◽  
Left Atrial ◽  
Right Atrial ◽  
Conduction Time ◽  
The Mean ◽  
Minimal Mass ◽  
Experimental Arrhythmia

With the aid of electrical stimulation and a combination of acetylcholine and physostigmine, an experimental arrhythmia was predictably induced in isolated atrial segments from rabbits. The tissue was from either left or right atrium, but was not spontaneously active. It was driven electrically at the rate of 2/sec. After the measurement of excitability and of conduction time, both in the presence and absence of ACh, an arrhythmia was induced. The tissue then was divided surgically and the procedure repeated until a residual segment was obtained which did not respond with an arrhythmia. The weight of the nonarrhythmic segment was determined and averaged 32 mg in 16 left atrial preparations, 28 mg in 10 right atrial segments, and 38 mg in 4 segments of left atrium from rabbits chronically treated with reserpine. Calculation of the mean conduction time and of the mean refractory period associated with induction of the experimental arrhythmia indicated that the observed minimal arrhythmic segment was approximately the mass theoretically required if the initiation and maintenance of the arrhythmia were dependent on re-entry excitation.

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