Radulescu, Anca R

Scimemi, Annalisa

Williams, Cassandra

English

VCU Scholars Compass

Virginia Commonwealth University VCU Scholars Compass Biology and Medicine Through Mathematics Conference Geometry-based estimates of glutamate transporter density in astrocytes Anca R. Radulescu State University of New York at New Paltz, radulesa@newpaltz.edu Cassandra Williams SUNY New Paltz, williamc18@hawkmail.newpaltz.edu Annalisa Scimemi University at Albany, scimemia@gmail.com Follow this and additional works at: https://scholarscompass.vcu.edu/bamm  Part of the Life Sciences Commons, Medicine and Health Sciences Commons, and the Physical Sciences and Mathematics Commons https://scholarscompass.vcu.edu/bamm/2020/poster/5 This Event is brought to you for free and open access by the Dept. of Mathematics and Applied Mathematics at VCU Scholars Compass. It has been accepted for inclusion in Biology and Medicine Through Mathematics Conference by an authorized administrator of VCU Scholars Compass. For more information, please contact libcompass@vcu.edu. Geometry-based estimates of glutamate transporter density in astrocytesAnca Raˇdulescu, SUNY New Paltz, radulesa@newpaltz.eduCassandra Williams, SUNY New Paltz, williamc18@hawkmail.newpaltz.eduAnnalisa Scimemi, University at Albany, scimemia@gmail.comGlutamate is the main excitatory neurotransmitter released in the brain. Its removal from the extracellular space isimportant to terminate synaptic transmission between neurons, and prevent build-up of neurotoxicity. The removalprocess is intermediated by non-neuronal cells called astrocytes. These take in the excess extracellular glutamate viatiny cross-membrane transporters densely expressed in the wall of the cell membrane. To understand their impact onneurotransmission efficiency, one needs to estimate the density of transporters for an average astrocyte [1, 2].Existing computations are based on simplifying assumptions of spherical cellular shape. However, the actual, 3-dimensional fractal geometry of a typical astrocyte may drastically reduce this number, due to the rigidity im-plied by the condition that transporters cannot collide with each other. We use a geometric modeling argument,based on the known crystal structure of the transporter, to study howthe structural complexity of astrocytic processes influences the sur-face density of transporters. Making only basic simplifying assump-tions of regularity and symmetry for the cell geometry, we considera cell model built around a spherical soma, surrounded by a three-dimensional branching tree. The geometry of the branching processesfollows certain spatial restrictions, and the length and diameter of thebranches depend on their position in the tree (e.g., generational dis-tance from the soma). The transporters can be well approximated to have prismatic shape, with an equilateraltriangular base. Using a combination of trigonometry and a variety of traditional and new integration algorithms, wecompute the number and fraction of the cellular membrane occupied by transporters, under the geometric constraintthat the intra-cellular ends of the transporters cannot meet.We compare our results to existing empirically-based estimates based on assumptions of simpler geometry, and wediscuss the significance of the improvement that geometrically-informed estimated may bring to the field. We useMonte Carlo reaction-diffusion simulations to determine whether our theoretical estimates challenge our knowledge ofhow glutamate transporters shape efficiency of synaptic transmission.References[1] J.S. Diamond. Deriving the glutamate clearance time course from transporter currents in CA1 hippocampalastrocytes: transmitter uptake gets faster during development. The Journal of Neuroscience, 25(11) 2906-2916,2005.[2] A. Scimemi et al. Neuronal transporters regulate glutamate clearance, NMDA receptor activation, and synapticplasticity in the hippocampus. The Journal of Neuroscience, 29(46) 14581-14595, 2009.1

Geometry-based estimates of glutamate transporter density in astrocytes

https://scholarscompass.vcu.edu/cgi/viewcontent.cgi?article=1395&amp;context=bamm

Geometry-based estimates of glutamate transporter density in astrocytes

Abstract

Similar works

Full text

Available Versions

VCU Scholars Compass