Building a bilayer model of the neuromuscular synapse

被引:5
作者
Woodbury D.J. [1 ]
机构
[1] Department of Physiology, Wayne Stt. Univ. School of Medicine, Detroit, MI
基金
美国国家卫生研究院;
关键词
ACh; AChR; synaptic vesicle; Ca; -channel; vesicle fusion; reconstitution;
D O I
10.1007/BF02738117
中图分类号
学科分类号
摘要
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.
引用
收藏
页码:303 / 329
页数:26
相关论文
共 74 条
[1]  
Rand, R.P., Parsegian, V.A., Mimicry and mechanism in phospholipid models of membrane fusion (1986) Ann. Rev. Physiol., 48, pp. 201-212
[2]  
Woodbury, D.J., Hall, J.E., Role of channels in the fusion of vesicles with a planar bilayer (1988) Biophys. J., 54, pp. 1053-1063
[3]  
Woodbury, D.J., Vesicle-membrane fusion detected by simultaneous electrical and optical measurements (1990) Proc. Twelfth Ann. Int. Conf. IEEE Eng. Med. Biol. Soc., 12, pp. 1747-1748
[4]  
Woodbury, D.J., Hall, J.E., Vesicle-membrane fusion: Observation of simultaneous content release and membrane incorporation (1988) Biophys. J., 54, pp. 345-349
[5]  
Cohen, F.S., Niles, W.D., Akabas, M.H., Fusion of phospholipid vesicles with a planar membrane depends on the membrane permeability of the solute used to create the osmotic pressure (1989) J. Gen. Phys., 93, pp. 201-210
[6]  
Nues, W.D., Cohen, F.S., Finkelstein, A., Hydrostatic pressures developed by osmotically swelling vesicles bound to planar membranes (1989) J. Gen. Phys., 93, pp. 211-244
[7]  
Woodbury, D.J., Miller, C., Nystatin-induced liposome fusion: A versatile approach to ion channel reconstitution into planar bilayers (1990) Biophys. J., 58, pp. 833-839
[8]  
Kelly, M.L., Woodbury, D.J., Ion channels from cholinergic synaptic vesicle fragments reconstituted into lipid bilayers (1996) Biophys. J., 70, pp. 2593-2599
[9]  
Woodbury, D.J., Nystatin/Ergosterol method for reconstituting ion channels into planar liquid bilayers (1998) Meth. Enzymol., 294, pp. 319-339
[10]  
Stiles, J.R., Helden, D.V., Bartol T.M., Jr., Salpeter, E.E., Salpeter, M.M., Miniature endplate current rise times less than 100 microseconds from improved dual recordings can be modeled with passive acetylcholine diffusion from a synaptic vesicle (1996) Proc. Natl. Acad. Sci. USA, 93, pp. 5747-5752