Building a bilayer model of the neuromuscular synapse.
Progress over the past 10 years has made it possible to construct a simple model of neurotransmitter release. Currently, some models use artificially formed vesicles to represent synaptic vesicles and a planar lipid bilayer as a presynaptic membrane. Fusion of vesicles with the bilayer is via channel proteins in the vesicle membrane and an osmotic gradient. In this paper; a framework is presented for the successful construction of a more complete model of synaptic transmission. This model includes real synaptic vesicles that fuse with a planar bilayer. The bilayer contains acetylcholine receptor (AChR) channels which function as autoreceptors in the membrane. Vesicle fusion is initiated following a Ca2+ flux through voltage-gated Ca2+ channels. Key steps in the plan are validated by mathematical modeling. Specifically, the probability that a reconstituted AChR channel opens following the release of ACh from a fusing vesicle, is calculated as a function of time, quantal content, and number of reconstituted AChRs. Experimentally obtainable parameters for construction of a working synapse are given. The inevitable construction of a full working model will mean that the minimal structures necessary for synaptic transmission are identified. This will open the door in determining regulatory and modulatory factors of transmitter release.
Woodbury
D J
DJ
Department of Physiology, Wayne State University School of Medicine, Detroit, MI, USA.
D000109:Acetylcholine / Q000378:metabolism; D015220:Calcium Channels / Q000502:physiology; D002135:Calcium-Binding Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008563:Membrane Lipids / Q000502:physiology; D008959:Models, Neurological; D009010:Monte Carlo Method; D009469:Neuromuscular Junction / Q000502:physiology*; D011950:Receptors, Cholinergic / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology*; D013572:Synaptic Vesicles / Q000502:physiology; D013997:Time Factors
D015220:Calcium Channels; D002135:Calcium-Binding Proteins; D008563:Membrane Lipids; D011950:Receptors, Cholinergic; D000109:Acetylcholine