scholarly journals Suppression of mICAT in Mouse Small Intestinal Myocytes by General Anaesthetic Ketamine and its Recovery by TRPC4 Agonist (-)-englerin A

2020 ◽  
Vol 11 ◽  
Author(s):  
Mariia I. Melnyk ◽  
Dariia O. Dryn ◽  
Lina T. Al Kury ◽  
Dmytro O. Dziuba ◽  
Alexander V. Zholos
Keyword(s):  
Negative Impact ◽  
Receptor Activation ◽  
General Anaesthetic ◽  
General Anesthetics ◽  
Englerin A ◽  
Cationic Current ◽  
Channel Opening ◽  
Trpc4 Channel ◽  
Novel Target ◽  
Kinetics Of

A better understanding of the negative impact of general anesthetics on gastrointestinal motility requires thorough knowledge of their molecular targets. In this respect the muscarinic cationic current (mICAT carried mainly via TRPC4 channels) that initiates cholinergic excitation-contraction coupling in the gut is of special interest. Here we aimed to characterize the effects of one of the most commonly used “dissociative anesthetics”, ketamine, on mICAT. Patch-clamp and tensiometry techniques were used to investigate the mechanisms of the inhibitory effects of ketamine on mICAT in single mouse ileal myocytes, as well as on intestinal motility. Ketamine (100 µM) strongly inhibited both carbachol- and GTPγS-induced mICAT. The inhibition was slow (time constant of about 1 min) and practically irreversible. It was associated with altered voltage dependence and kinetics of mICAT. In functional tests, ketamine suppressed both spontaneous and carbachol-induced contractions of small intestine. Importantly, inhibited by ketamine mICAT could be restored by direct TRPC4 agonist (-)-englerin A. We identified mICAT as a novel target for ketamine. Signal transduction leading to TRPC4 channel opening is disrupted by ketamine mainly downstream of muscarinic receptor activation, but does not involve TRPC4 per se. Direct TRPC4 agonists may be used for the correction of gastrointestinal disorders provoked by general anesthesia.

scholarly journals Desensitization Contributes to the Synaptic Response of Gain-of-Function Mutants of the Muscle Nicotinic Receptor

2006 ◽  
Vol 128 (5) ◽  
pp. 615-627 ◽  
Author(s):  
Sergio Elenes ◽  
Ying Ni ◽  
Gisela D. Cymes ◽  
Claudio Grosman
Keyword(s):  
Nicotinic Receptor ◽  
Dissociation Rate ◽  
Gain Of Function ◽  
Naturally Occurring ◽  
Channel Opening ◽  
Speed Up ◽  
High Concentrations ◽  
Dissociation Rate Constants ◽  
Kinetics Of ◽  
Peak Value

Although the muscle nicotinic receptor (AChR) desensitizes almost completely in the steady presence of high concentrations of acetylcholine (ACh), it is well established that AChRs do not accumulate in desensitized states under normal physiological conditions of neurotransmitter release and clearance. Quantitative considerations in the framework of plausible kinetic schemes, however, lead us to predict that mutations that speed up channel opening, slow down channel closure, and/or slow down the dissociation of neurotransmitter (i.e., gain-of-function mutations) increase the extent to which AChRs desensitize upon ACh removal. In this paper, we confirm this prediction by applying high-frequency trains of brief (∼1 ms) ACh pulses to outside-out membrane patches expressing either lab-engineered or naturally occurring (disease-causing) gain-of-function mutants. Entry into desensitization was evident in our experiments as a frequency-dependent depression in the peak value of succesive macroscopic current responses, in a manner that is remarkably consistent with the theoretical expectation. We conclude that the comparatively small depression of the macroscopic currents observed upon repetitive stimulation of the wild-type AChR is due, not to desensitization being exceedingly slow but, rather, to the particular balance between gating, entry into desensitization, and ACh dissociation rate constants. Disruption of this fine balance by, for example, mutations can lead to enhanced desensitization even if the kinetics of entry into, and recovery from, desensitization themselves are not affected. It follows that accounting for the (usually overlooked) desensitization phenomenon is essential for the correct interpretation of mutagenesis-driven structure–function relationships and for the understanding of pathological synaptic transmission at the vertebrate neuromuscular junction.

Desensitization and resensitization rates of glutamate-activated channels may regulate motoneuron excitability

1991 ◽  
Vol 66 (4) ◽  
pp. 1166-1175 ◽  
Author(s):  
D. O. Smith ◽  
C. Franke ◽  
J. L. Rosenheimer ◽  
F. Zufall ◽  
H. Hatt
Keyword(s):  
Ampa Receptors ◽  
Single Channel ◽  
Kainate Receptors ◽  
Whole Cell ◽  
Solution Exchange ◽  
Channel Opening ◽  
Fast Solution ◽  
Agonist Concentration ◽  
Kinetics Of ◽  
Channel Properties

1. Single-channel properties of desensitizing glutamate-activated channels were analyzed in outside-out patch-clamp recordings from a motoneuron-enriched cell fraction from embryonic chick. A piezo-driven device was used to achieve fast solution exchange at the electrode tip, resulting in maximum activation within 2 ms. 2. Quisqualate/AMPA receptors, with a 13-pS conductance, desensitized rapidly; the desensitization rate depended on agonist concentration but not on membrane potential. When quisqualate was applied slowly, the quisqualate-activated channels desensitized without prior channel opening, indicating desensitization from the closed state. After a 10-ms refractory period, resensitization of all channels required up to 300 ms; resensitization rate did not depend on the duration of the preceding quisqualate application. 3. At agonist concentrations less than or equal to 1 mM, kainate receptors, with a 20-pS conductance, did not desensitize. At kainate concentrations greater than or equal to 1 mM, though, kainate receptors desensitized to a low steady-state conductance within approximately 200 ms. Resensitization of all channels required as long as 3 s, which could render kainate receptors inexcitable during high-frequency activation. 4. Desensitization rates of whole-cell currents were similar to those observed in outside-out mode. Glutamate- and quisqualate-activated responses were similar, suggesting that the rapidly desensitizing quisqualate-sensitive receptor type may dominate the kinetics of whole-cell excitatory postsynaptic currents (EPSCs) in this preparation. 5. It may be concluded that the efficacy of glutamate-mediated synaptic transmission is modulated by differences in the rates of desensitization and resensitization.

scholarly journals CHARACTERIZATION AND STUDY OF THE KINETICS OF SEDIMENTATION OF REJECT OF THE IRON ORE INDUSTRY

2018 ◽  
Vol 15 (30) ◽  
pp. 647-653
Author(s):  
J. H. M. SANTOS ◽  
P. C. M. SANTOS ◽  
F. T. VIEIRA ◽  
J. D. FABRIS ◽  
A. B. REIS ◽  
...  
Keyword(s):  
Iron Ore ◽  
Negative Impact ◽  
Mining Industry ◽  
Water Recovery ◽  
Recycle Water ◽  
Industrial Activity ◽  
The Earth ◽  
Energy Spectrometer ◽  
Kinetics Of ◽  
Scanning Electron

Currently the mining industry plays an important role in the generation of wealth of a country through the exploitation of natural resources of the earth, and in some cases, responsible for a significant fraction of the economic matrix. Like any other industrial activity, mining has a negative impact on the environment, which leads the industry to constantly face the challenge of achieving the sustainability of its activities. The study aimed to characterize the iron ore reject seeking the feasibility of reprocessing and water recovery. The reject sample was characterized using Scanning Electron Microscopy with Dispersive Energy Spectrometer. Studies of the sedimentation kinetics of the tailings were carried out to implement techniques to recover the iron present in the tailings and recycle water in the mineral processing. In the sedimentation tests it was possible to recover approximately 50% of water without compromising the transport operations of the material. It can be concluded that the ore reject analyzed is composed mainly of Fe and Si respectively, showing that the reject has reprocessing potential, and recovery of water present in the clarified.

scholarly journals The analgesic effect of dipyrone in peripheral tissue involves two different mechanisms: Neuronal KATP channel opening and CB1 receptor activation

2014 ◽  
Vol 741 ◽  
pp. 124-131 ◽  
Author(s):  
Gilson Gonçalves dos Santos ◽  
Elayne Vieira Dias ◽  
Juliana Maia Teixeira ◽  
Maria Carolina Pedro Athie ◽  
Ivan José Magayewski Bonet ◽  
...  
Keyword(s):  
Analgesic Effect ◽  
Katp Channel ◽  
Receptor Activation ◽  
Cb1 Receptor ◽  
Peripheral Tissue ◽  
Channel Opening

Pungency of TRPV1 agonists is directly correlated with kinetics of receptor activation and lipophilicity

2010 ◽  
Vol 641 (2-3) ◽  
pp. 114-122 ◽  
Author(s):  
Daniel Ursu ◽  
Kelly Knopp ◽  
Ruth E. Beattie ◽  
Bin Liu ◽  
Emanuele Sher
Keyword(s):  
Receptor Activation ◽  
Kinetics Of

scholarly journals Kinetics of Biotic and Abiotic CO Production during the Initial Phase of Biowaste Composting

Energies ◽  
2020 ◽  
Vol 13 (20) ◽  
pp. 5451
Author(s):  
Sylwia Stegenta-Dąbrowska ◽  
Karolina Sobieraj ◽  
Jacek A. Koziel ◽  
Jerzy Bieniek ◽  
Andrzej Białowiec
Keyword(s):  
Initial Phase ◽  
Occupational Safety ◽  
Negative Impact ◽  
Order Kinetic ◽  
K Value ◽  
Thermochemical Process ◽  
Full Study ◽  
Order Kinetic Model ◽  
First Time ◽  
Kinetics Of

Knowledge of kinetic parameters of CO production during biowaste composting is significantly important for the prediction of its course and estimation of total gas quantity. This allows increasing the control of the process, to minimize its negative impact on the environment and to protect the occupational safety of employees exposed to CO in the biowaste composting plant. For the first time, a full study of the influence of temperature and biowaste sterilization on the kinetics of CO production is presented. The lab-scale experiments used a mixture of green waste, dairy cattle manure, and sawdust in two variants: sterilized and non-sterilized samples. The process was carried out in controlled temperature reactors with measuring the concentrations of CO, O2, and CO2 every 12 h.CO production and k value increased with temperature. However, higher CO production was observed in biotic conditions between 10~50 °C, suggesting the biotic CO formation and 1st-order kinetics. The abiotic (thermochemical) process was more efficiently generating CO above 50 °C, described with a 0-order kinetic model. Additionally, the rate constant (k) value of CO production under biotic conditions was increasing up to a temperature of 60 °C, above which a slight decrease in CO production rate was observed at 70 °C. The presented results are the basis for further studies focused on the feasibility of (1) the mitigation and (2) valorization of CO production during the biowaste biostabilization are warranted.

Kinetics of calcium channel opening by inositol 1,4,5-trisphosphate

Biochemistry ◽  
1990 ◽  
Vol 29 (1) ◽  
pp. 32-37 ◽  
Author(s):  
Tobias Meyer ◽  
Theodore Wensel ◽  
Lubert Stryer
Keyword(s):  
Calcium Channel ◽  
Channel Opening ◽  
Inositol 1,4,5 Trisphosphate ◽  
Kinetics Of
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