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.
Department of Physiology, Wayne State University School of Medicine, Detroit, MI, USA.
D J
DJ
Woodbury
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