Untitled

Pawson, Peter A.; Grinnell, Alan D.; Wolowske, Birgit

doi:10.1023/a:1006995010453

Cited by 12 publications

(1 citation statement)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Each AZ is a highly organized structure consisting of two long rows of 20–40 docked synaptic vesicles. The gap between these rows of synaptic vesicles contains two highly ordered double rows of 200–250 intramembranous particles ( Figure 1C ) (Heuser et al, 1974 , 1979 ; Pawson et al, 1998 ). Despite the presence of 12,000–24,000 docked vesicles in the ~600 AZs, a presynaptic action potential triggers the release of neurotransmitter from only about 200–500 synaptic vesicles (mean = 415) (Laghaei et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Microphysiological Modeling of the Structure and Function of Neuromuscular Transmitter Release Sites

Laghaei

Meriney

2022

Front. Synaptic Neurosci.

View full text Add to dashboard Cite

The general mechanism of calcium-triggered chemical transmitter release from neuronal synapses has been intensely studied, is well-known, and highly conserved between species and synapses across the nervous system. However, the structural and functional details within each transmitter release site (or active zone) are difficult to study in living tissue using current experimental approaches owing to the small spatial compartment within the synapse where exocytosis occurs with a very rapid time course. Therefore, computer simulations offer the opportunity to explore these microphysiological environments of the synapse at nanometer spatial scales and on a sub-microsecond timescale. Because biological reactions and physiological processes at synapses occur under conditions where stochastic behavior is dominant, simulation approaches must be driven by such stochastic processes. MCell provides a powerful simulation approach that employs particle-based stochastic simulation tools to study presynaptic processes in realistic and complex (3D) geometries using optimized Monte Carlo algorithms to track finite numbers of molecules as they diffuse and interact in a complex cellular space with other molecules in solution and on surfaces (representing membranes, channels and binding sites). In this review we discuss MCell-based spatially realistic models of the mammalian and frog neuromuscular active zones that were developed to study presynaptic mechanisms that control transmitter release. In particular, these models focus on the role of presynaptic voltage-gated calcium channels, calcium sensors that control the probability of synaptic vesicle fusion, and the effects of action potential waveform shape on presynaptic calcium entry. With the development of these models, they can now be used in the future to predict disease-induced changes to the active zone, and the effects of candidate therapeutic approaches.

show abstract

Section: Introductionmentioning

confidence: 99%

Microphysiological Modeling of the Structure and Function of Neuromuscular Transmitter Release Sites

Laghaei

Meriney

2022

Front. Synaptic Neurosci.

View full text Add to dashboard Cite

show abstract

Sensitivity of Intracellular Calcium-Binding Sites for Exo- and Endocytosis of Synaptic Vesicles to Sr, Ba, and Mg Ions

Зефиров

Grigor'ev

2010

Neurosci Behav Physi

View full text Add to dashboard Cite

Experiments on frog cutaneous-thoracic muscle preparations using electrophysiological (intra- and extracellular recording of postsynaptic signals) and optical (confocal microscopy with the fluorescent endocytic stain FM 1-43) methods were performed to study neurotransmitter secretion and the processes of exo- and endocytosis of synaptic vesicles in motor nerve endings on substitution of extracellular Ca ions with other alkaline earth metals (Sr, Ba, or Mg). Massive asynchronous exocytosis was induced by high-potassium solution, while synchronous exocytosis was induced by prolonged high-frequency stimulation of the motor nerve. The calcium-binding site for asynchronous exocytosis was found to be sensitive to Sr, Ba, and Mg ions, while the site for synchronous exocytosis was only sensitive to Sr ions. During stimulation of both asynchronous and synchronous exocytosis, the calcium-binding site for endocytosis was sensitive to Sr and Ba ions and had the lowest affinity for Sr ions. These experiments led to the conclusion that different intracellular calcium-binding sites exist for the exocytosis and endocytosis of synaptic vesicles and that they have different sensitivities for alkaline earth metals.

show abstract

Structural and Functional Maturation of Active Zones in Large Synapses

et al. 2012

View full text Add to dashboard Cite

Virtually all functions of the nervous system rely upon synapses, the sites of communication between neurons and between neurons and other cells. Synapses are complex structures, each one comprising hundreds of different types of molecules working in concert. They are organized by adhesive and scaffolding molecules that align presynaptic vesicular release sites, namely, active zones, with postsynaptic neurotransmitter receptors, thereby allowing rapid and reliable intercellular communication. Most synapses are relatively small, and acting alone exerts little effect on their postsynaptic partners. Some, however, are much larger and stronger, reliably driving the postsynaptic cell to its action potential threshold, acting essentially as electrical relays of excitation. These large synapses are among the best understood, and two of these are the subject of this review, namely, the vertebrate neuromuscular junction and the calyx of Held synapse in the mammalian auditory pathway of the brain stem. Both synapses undergo through a complex and well-coordinated maturation process, during which time the molecular elements and the biophysical properties of the secretory machinery are continuously adjusted to the synapse size and to the functional requirements. We here review the morphological and functional changes occurring during postnatal maturation, noting particular similarities and differences between these two large synapses.

show abstract

Untitled

Cited by 12 publications

References 43 publications

Microphysiological Modeling of the Structure and Function of Neuromuscular Transmitter Release Sites

Microphysiological Modeling of the Structure and Function of Neuromuscular Transmitter Release Sites

Sensitivity of Intracellular Calcium-Binding Sites for Exo- and Endocytosis of Synaptic Vesicles to Sr, Ba, and Mg Ions

Structural and Functional Maturation of Active Zones in Large Synapses

Contact Info

Product

Resources

About