Abstract
We have developed a biophysically realistic model of receptor activation
at an idealized central glutamatergic synapse that uses Monte Carlo
techniques to simulate the stochastic nature of transmission following
release of a single synaptic vesicle. For the a synapse with 80 AMPA
and 20 NMDA receptors, a single quantum, with 3000 glutamate molecules,
opened approximately 3 NMDARs and 20 AMPARs. The number of open receptors
varied directly with the total number of receptors, and the fraction
of open receptors did not depend on the ratio of co-localized AMPARs
and NMDARs. Variability decreased with increases in either total
receptor number or quantal size, and differences between the variability
of AMPAR and NMDAR responses were due solely to unequal numbers of
receptors at the synapse. Despite NMDARs having a much higher affinity
for glutamate than AMPARs, quantal release resulted in similar occupancy
levels in both receptor types. Receptor activation increased with
number of transmitter molecules released or total receptor number,
whereas occupancy levels were only dependent on quantal size. Tortuous
diffusion spaces reduced the extent of spillover and the activation
of extrasynaptic receptors. These results support the conclusion
that signaling is spatially independent within and between central
glutamatergic synapses.
- 12414671
- acid,
- animals,
- biological
- carlo
- central
- chemical,
- factors,
- glutamic
- gov't,
- kinetics,
- method,
- models,
- monte
- n-methyl-d-aspartate,
- nervous
- non-p.h.s.,
- non-u.s.
- port,
- receptors,
- research
- signal
- sup,
- support,
- synapses,
- system,
- time
- transduction,
- transport,
- u.s.
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