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Title Calculation of open probabilities of AMPA and NMDA receptors located at various distances from the glutamate release site
Free Keywords NG-Model
Item Description Abstract / Acknowledgment --- SDS-freeze replica labeling (SDS-FRL) method can reveal two-dimensional distribution of molecules along the plasma membrane such as receptors for sensing neurotransmitters. Work from Dr. Ryuichi Shigemoto’s lab has uncovered various interesting ways neurons and glial cells strategically distribute receptors. They found areas with dense and sparse receptor distribution, and they also found heterogeneity of receptors distribution even within a single cluster of receptors. However, without knowing 1) the time course of transmitter concentration at the location of receptors and 2) the kinetics of receptor opening responding to such concentration change, the physiological significance of receptor distribution cannot be determined. Here, I developed a method for calculating glutamate diffusion within the synaptic cleft and suggest a simple solution for calculating open probabilities of AMPA and NMDA receptors. The programs used are commercially available ones such as Microsoft Excel and AxoGraph (http://axographx.com/). Method described can be modified to any other transmitter and receptor combination, given that the diffusion characteristics and the kinetic properties of the receptors are known. The limitation of this method is that only two-dimensional diffusion is considered. Therefore, only locations where two plasma membranes parallel each other for some distance can be simulated, such as the synaptic cleft. In addition, transporters and such that would buffer the diffusion are not taken into account. For more accurately modeling transmitter diffusion in three-dimensional space with multiple factors for modifying diffusion, the use of Monte-Carlo simulation, such as the one provided by M-Cell (http://www.mcell.cnl.salk.edu/) should be considered. Still, the method I show would be useful in quickly giving insights on how the distribution of receptors affects synaptic transmission. The method described has been used to analyze characteristics of glutamatergic synaptic transmission at retinogeniculate and corticogeniculate synapses in the dorsal lateral geniculate nuleus (E. Tarusawa, Y. Fukazawa, K. Matsui, R. Shigemoto. Unpublished data.).

Affiliation / E-mail --- Division of Cerebral Structure, National Institute for Physiological Sciences, Okazaki, Aichi 444-8787, Japan. (Correspondence: matsui@nips.ac.jp)
Last Modified Date Oct 29, 2009 11:31:10
Created Date Oct 29, 2009 11:31:10
Contributor DBPF Administrator 1 (admin)
Item Type Model
Change Log(History)
Model type Other
Ko Matsui
Ryuichi Shigemoto
Glutamate diffusion and AMPA NMDA receptor openings
Glutamate diffusion and AMPA NMDA receptor openings
Model file KMDiffusion.zip 10660 bytes   (Login User only)
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