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Critical Reviews™ in Neurobiology

Publicado 3 números por año

ISSN Imprimir: 0892-0915

ISSN En Línea: 2375-0014

SJR: 0.121

Molecular Dynamics Simulations of Glutamate Diffusion in Synaptic Cleft

Volumen 18, Edición 1-2, 2006, pp. 61-69
DOI: 10.1615/CritRevNeurobiol.v18.i1-2.70
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SINOPSIS

Diffusion of transmitters in the synaptic cleft critically influences synaptic efficacy by affecting both the amplitude and the time course of quantal events, but the value of the diffusion constant is speculative. In this study, we use molecular dynamics simulations to determine how the spatial confinement and membrane charges affect the diffusion constants of glutamate- and water as well as general properties of their diffusion. The synaptic cleft is represented as the space enclosed by two single-wall carbon sheets. Both water and especially glutamate are concentrated near the pore wall, where the concentration of glutamate can reach 30-50 times the mean value and the concentration of water can reach 2-8 times the mean value. Such spatial profiles of glutamate contradict the classical notions of diffusion on which both continuous and Monte Carlo simulations are built. The layering of glutamate- and water molecules suggests that the interfacial glutamate-cleft wall (or water-cleft wall) interactions may critically regulate their diffusion in the cleft. Indeed, the effective longitudinal diffusion constant of glutamate is steeply dependent on the cleft width, but only when the cleft is very narrow (< 5 nm). Therefore, even for a cleft as narrow as at the glutamatergic synapse in the central nervous system, the effective diffusion constant of glutamate will not be much lower than free diffusion in the bulk solution due to confinement. The effective diffusion constant of water is considerably less sensitive to cleft width over the same range of cleft widths than is glutamate, but is also higher than that of glutamate. Finally, the layering of glutamate and water and their effective diffusion constants are largely independent of how the cleft wall is charged. In conclusion, in the confined space of the synaptic cleft, glutamate is layered near the wall. Consequently, its diffusion constant becomes dependent on the cleft width. However, the diffusion of glutamate is slower than its free diffusion in water only if the cleft is very narrow. If the width of the cleft is consistent with that determined by morphometric studies in the central nervous system, glutamate diffusion should not be slowed by confinement and is thus likely to be similar to that in free solution.

CITADO POR
  1. Stone Emily, Hoffman Katie, Kavanaugh Michael, Identifying neurotransmitter spill-over in hippocampal field recordings, Mathematical Biosciences, 240, 2, 2012. Crossref

  2. Gupta Rahul, Reneaux Melissa, Karmeshu , Xu Jianhua, Role of Heterogeneous Macromolecular Crowding and Geometrical Irregularity at Central Excitatory Synapses in Shaping Synaptic Transmission, PLOS ONE, 11, 12, 2016. Crossref

  3. Di Maio Vito, Santillo Silvia, Ventriglia Francesco, Multisynaptic cooperation shapes single glutamatergic synapse response, Brain Research, 1697, 2018. Crossref

  4. Di Maio Vito, Santillo Silvia, Ventriglia Francesco, Synaptic dendritic activity modulates the single synaptic event, Cognitive Neurodynamics, 15, 2, 2021. Crossref

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