Kinetic modelling of processes in the cholinergic synapse. Mechanisms of functioning and control methods

2020 ◽  
pp. 127-139
Author(s):  
Sergey Varfolomeev ◽  
Viktor Bykov ◽  
Svetlana Tsybenova

The kinetic model describing the dynamics of synaptic “discharge” taking into account the kinetics of the injection of the neurotransmitter into the synaptic cleft, the pH-dependence of catalytic activity of the enzyme and diffusion withdrawal of protons is proposed and studied. In the framework of the kinetic model, the functioning of the cholinergic synapse is considered. The results of mathematical modeling of changes in the level of acetylcholine, induced pH impulse, the influence of the frequency of impulse transfer and inhibition of acetylcholinesterase are presented. Physico-chemical explanation for a number of important physiological phenomena, such as neuromuscular paralysis, the molecular mechanism of neurological memory, actions of nerve poisons and toxins and Alzheimer’s disease is given.

Author(s):  
Sergey Varfolomeev ◽  
Viktor Bykov ◽  
Svetlana Tsybenova

The kinetic model describing the dynamics of synaptic “discharge” taking into account the kinetics of the injection of the neurotransmitter into the synaptic cleft, the pH-dependence of catalytic activity of the enzyme and diffusion withdrawal of protons is proposed and studied. In the framework of the kinetic model, the functioning of the cholinergic synapse is considered. The results of mathematical modeling of changes in the level of acetylcholine, induced pH impulse, the influence of the frequency of impulse transfer and inhibition of acetylcholinesterase are presented. Physico-chemical explanation for a number of important physiological phenomena, such as neuromuscular paralysis, the molecular mechanism of neurological memory, actions of nerve poisons and toxins and Alzheimer’s disease is given.


Author(s):  
S. Varfolomeev ◽  
V. Bykov

A kinetic model describing the dynamics of synaptic "discharge" taking into account the kinetics of neurotransmitter release into a synaptic cleft, pH-dependence of the enzyme catalytic activity and diffusion proton removal has been proposed and studied.


1986 ◽  
Vol 237 (1) ◽  
pp. 217-227 ◽  
Author(s):  
G W Gould ◽  
J M East ◽  
R J Froud ◽  
J M McWhirter ◽  
H I Stefanova ◽  
...  

The Ca2+ + Mg2+-activated ATPase of sarcoplasmic reticulum exhibits complex kinetics of activation with respect to ATP. ATPase activity is pH-dependent, with similar pH-activity profiles at high and low concentrations of ATP. Low concentrations of Ca2+ in the micromolar range activate the ATPase, whereas activity is inhibited by Ca2+ at millimolar concentrations. The pH-dependence of this Ca2+ inhibition and the effect of the detergent C12E8 (dodecyl octaethylene glycol monoether) on Ca2+ inhibition are similar to those observed on activation by low concentrations of Ca2+. On the basis of these and other studies we present a kinetic model for the ATPase. The ATPase is postulated to exist in one of two conformations: a conformation (E1) of high affinity for Ca2+ and MgATP and a conformation (E2) of low affinity for Ca2+ and MgATP. Ca2+ binding to E2 and to the phosphorylated form E2P are equal. Proton binding at the Ca2+-binding sites in the E1 and E2 conformations explains the pH-dependence of Ca2+ effects. Binding of MgATP to the phosphorylated intermediate E1′PCa2 and to E2 modulate the rates of the transport step E1′PCa-E2′PCa2 and the return of the empty Ca2+ sites to the outside surface of the sarcoplasmic reticulum, as well as the rate of dephosphorylation of E2P. Only a single binding site for MgATP is postulated.


2012 ◽  
Vol 33 (4) ◽  
pp. 651-665 ◽  
Author(s):  
Marta Pawlak ◽  
Marcin Bizukojć

A kinetic model to describe lovastatin biosynthesis by Aspergillus terreus ATCC 20542 in a batch culture with the simultaneous use of lactose and glycerol as carbon sources was developed. In order to do this the kinetics of the process was first studied. Then, the model consisting of five ordinary differential equations to balance lactose, glycerol, organic nitrogen, lovastatin and biomass was proposed. A set of batch experiments with a varying lactose to glycerol ratio was used to finally establish the form of this model and find its parameters. The parameters were either directly determined from the experimental data (maximum biomass specific growth rate, yield coefficients) or identified with the use of the optimisation software. In the next step the model was verified with the use of the independent sets of data obtained from the bioreactor cultivations. In the end the parameters of the model were thoroughly discussed with regard to their biological sense. The fit of the model to the experimental data proved to be satisfactory and gave a new insight to develop various strategies of cultivation of A. terreus with the use of two substrates.


2007 ◽  
Vol 293 (1) ◽  
pp. C228-C237 ◽  
Author(s):  
Nicole M. A. van den Broek ◽  
Henk M. M. L. De Feyter ◽  
Larry de Graaf ◽  
Klaas Nicolay ◽  
Jeanine J. Prompers

31P magnetic resonance spectroscopy provides the possibility of obtaining bioenergetic data during skeletal muscle exercise and recovery. The time constant of phosphocreatine (PCr) recovery (τPCr) has been used as a measure of mitochondrial function. However, cytosolic pH has a strong influence on the kinetics of PCr recovery, and it has been suggested that τPCr should be normalized for end-exercise pH. A general correction can only be applied if there are no intersubject differences in the pH dependence of τPCr. We investigated the pH dependence of τPCr on a subject-by-subject basis. Furthermore, we determined the kinetics of proton efflux at the start of recovery. Intracellular acidosis slowed PCr recovery, and the pH dependence of τPCr differed among subjects, ranging from −33.0 to −75.3 s/pH unit. The slope of the relation between τPCr and end-exercise pH was positively correlated with both the proton efflux rate and the apparent proton efflux rate constant, indicating that subjects with a smaller pH dependence of τPCr have a higher proton efflux rate. Our study implies that simply correcting τPCr for end-exercise pH is not adequate, in particular when comparing patients and control subjects, because certain disorders are characterized by altered proton efflux from muscle fibers.


Author(s):  
Harry A. Atwater ◽  
C.M. Yang ◽  
K.V. Shcheglov

Studies of the initial stages of nucleation of silicon and germanium have yielded insights that point the way to achievement of engineering control over crystal size evolution at the nanometer scale. In addition to their importance in understanding fundamental issues in nucleation, these studies are relevant to efforts to (i) control the size distributions of silicon and germanium “quantum dots𠇍, which will in turn enable control of the optical properties of these materials, (ii) and control the kinetics of crystallization of amorphous silicon and germanium films on amorphous insulating substrates so as to, e.g., produce crystalline grains of essentially arbitrary size.Ge quantum dot nanocrystals with average sizes between 2 nm and 9 nm were formed by room temperature ion implantation into SiO2, followed by precipitation during thermal anneals at temperatures between 30°C and 1200°C[1]. Surprisingly, it was found that Ge nanocrystal nucleation occurs at room temperature as shown in Fig. 1, and that subsequent microstructural evolution occurred via coarsening of the initial distribution.


2018 ◽  
Vol 69 (10) ◽  
pp. 2633-2637
Author(s):  
Raluca Dragomir ◽  
Paul Rosca ◽  
Cristina Popa

The main objectives of the present paper are to adaptation the five-kinetic model of the catalytic cracking process and simulation the riser to predicts the FCC products yields when one of the major input variable of the process is change. The simulation and adaptation are based on the industrial data from Romanian refinery. The adaptation is realize using a computational method from Optimization Toolbox from Matlab programming language. The new model can be used for optimization and control of FCC riser.


1986 ◽  
Vol 51 (10) ◽  
pp. 2098-2108 ◽  
Author(s):  
Milan Pospíšil ◽  
Jan Topinka

We investigated the effect of origin and some physico-chemical parameters on the kinetics of reduction with hydrogen of two series of mixed NiO-Fe2O3 oxides differing by their composition, the character of their precursors (mixed crystalline nitrates and coprecipitated hydroxides) and their decomposition temperature.This effect manifested itself by different magnitudes of specific surfaces of the mixed oxides and coherent regions of present phases as well as by different oxidizing abilities of the surface and differences in morphology and phase composition of corresponding samples in both series investigated. Nonlinear or nonmonotonous composition dependences of physico-chemical parameters investigated point to a mutual influence of individual components, which is also a function of the system origin and which modifies its reactivity during its reduction with hydrogen. The kinetics of the reduction was studied thermogravimetrically at 320-410 °C. The reduction of oxides of the hydroxide origin is catalytically accelerated by primarily reduced nickel, whereas in corresponding samples of the nitrate series, the total NiO is bound to the spinel phase and the reduction is delayed. Experimental IR spectra, the effect of preliminary annealing and DTA of the mixed oxides point to an inhibitory effect of water, which is constitutionally bound in trace admixtures of the goethite phase, on the kinetics of reduction of samples in the hydroxide series.


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