Kinetic modeling of dynamic processes in the cholinergic synapse
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Kinetic modeling of dynamic processes in the cholinergic synapse* S. D. Varfolomeev,a,b V. I. Bykov,b and S. B. Tsybenovab aInstitute
of Physicochemical Foundations of the Functioning of Neural Network and Artificial Intelligence, Lomonosov Moscow State University, 1 Leninskie Gory, 119991 Moscow, Russian Federation. Fax:+7 (499) 939 35 89 bN. M. Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, 4 ul. Kosygina, 119334 Moscow, Russian Federation. Fax: +7 (499) 137 4101. E-mail: [email protected] A kinetic model describing the dynamics of synaptic "discharge", taking into account the kinetics of the neurotransmitter injection into the synaptic cleft, pH dependence of the enzyme catalytic activity, and proton removal by diffusion was proposed and studied. In the framework of the kinetic model, functioning of the cholinergic synapse was considered. The results of mathematical modeling of the change in the acetylcholine level, induced pH impulse, and the effect of the impulse transmission frequency and acetylcholinesterase inhibition are presented. A physicochemical interpretation was given for a number of key important physiological phenomena, such as neuromuscular paralysis, the mechanism of information recording and storage in the neurological memory, the action of nerve poisons and toxins, and Alzheimer´s disease. Key words: kinetic model, process dynamics, human brain, acetylcholinesterase inhibition, acetylcholine, cholinergic synapse, Alzheimer´s disease.
Study of the behavior of the human brain neural network is an important challenge of modern natural science.1,2 Functioning of the system of neuronal junctions, synapses, during the impulse transmission from one neuron to another is the key process in the operation of the neural network of the brain. The diversity, the nature of synapses, and the mechanism of electrical impulse transmission are actively studied and extensively discussed in the literature.3—7 The systemic association of nerve cells that form brain as a biocomputer occurs through specialized macromolecular structures, which provide signal (nerve impulse) transmission from one neuron to another. Functioning of the central nervous system (CNS) is mediated by a large number of "chemical" synapses and neurotransmitters — small-molecule components injected from a donor cell to an acceptor cell via transfer and exposure, into the intercellular space (synaptic cleft), of the synaptic vesicles contained in the presynaptic neuron area. The process occurs via Ca2+-dependent exocytosis. Thus, a synapse is a macromolecular mechanical electrodynamic system operating in a definite frequency mode. The chemical nature of neurotransmitters is quite diverse. They include acetylcholine, aspartic and glutamic acids, glycine, -aminobutyric acid, histamine, noradrenaline, dopamine, serotonin, and some peptides. As * Dedicated to Academician of the Russian Academy of Sciences A. M. Muzafarov on the occasion of his 70th birthday.
a rule, a neurotransmitter diffuses in the synaptic cleft to
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