NACS641-10L4 - Synaptic transmission & NT release...

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Unformatted text preview: Synaptic transmission & NT release Ricardo C. Araneda Fall 2010 Sunday, September 19, 2010 What is a synapse? Sherrington late 1897 Loewi 1926, Vagusstoff (NP 1936) Dale 1926, Release of ACh at motor endings (NP 1936) Eccles 1952, First intracellular recording in MT. Did not believe originally in chemical transmission (NP 1936) Sunday, September 19, 2010 Types of synapses Sunday, September 19, 2010 Electrical synapses a giant synapse in the crayfish Rectification Furshpan & Porter 1959 Sunday, September 19, 2010 Synaptic delay in chemical and electrical synapses Chick ciliary ganglion cell ~ 2 ms delay at RT what about at 4 C? Martin & Pilar 1963 Sunday, September 19, 2010 The Neuromuscular junction was the classic preparation for understanding the basis for synaptic transmission in experiments in the 1960’s by Katz, Miledi and collaborators. Sunday, September 19, 2010 Presynaptic impulse and postsynaptic response Bullock & Hagiwara 1959 Katz & Miledi 1977 K and Na fluxes are not necessary for release only depolarization Sunday, September 19, 2010 Synaptic delay in chemical synapses Frog neuromuscular junction Diffusion of ACh in synaptic cleft (50 nm) ∼50 μs Delay mostly due to the NT release mechanism Katz & Miledi 1965 Sunday, September 19, 2010 Presynaptic Ca and NT release Squid giant synapse (in TTX and TEA) Ca enters near site of release Fast Llinas 1982 Sunday, September 19, 2010 Slow Adler et al. 1991 Quantal Release of NT The EPP is composed of quantal units that correspond to spontaneous mEPP Fat & Katz 1952 Sunday, September 19, 2010 Model proposed by Katz and del Castillo (1955) Confirmed by electron microscopy studies by Palay, Palade, deRobertis Sunday, September 19, 2010 Ultrastructure of Nerve Terminals Freeze fracture Heuser, Reese and Landis 1974 Vesicle exocytosis corresponds to quantal release Sunday, September 19, 2010 Sunday, September 19, 2010 Recycling of synaptic vesicle components Sunday, September 19, 2010 Stops involved in chemical synaptic transmission AP arrives V-dependent Ca2+ channels open NT released into Synaptic cleft NT binds to receptor Proteins – o pens channels Ions enter Postsynaptic cell -Change Postsynaptic Vm Sunday, September 19, 2010 Sunday, September 19, 2010 Models for synaptic release Sunday, September 19, 2010 Sunday, September 19, 2010 A model for 2+-triggered Ca vesicle fusion. -When contact with its partners is established, synaptobrevin rolls up into an a -helix, thereby pulling the vesicle membrane very close to the plasma membrane. -The energy released during this process is largely responsible for overcoming the barrier for fusion. -In neurons, fusion requires the influx of Ca ions that probably bind to the calcium binding protein synaptotagmin which in turn interacts with the SNAREs, probably g iving them the final twist for exocytosis. Sunday, September 19, 2010 Various ways of retrieving the SV membrane. 1- SVs could fuse and completely collapse into the presynaptic membrane and be retrieved by clathrin-mediated endocytosis. They could then be recycled through an endosomal compartment. 2- Clathrin-mediated endocytosis could be followed by direct recycling, without passage through early endosomes. 3- SVs might not fuse completely with the cell membrane, but might be rapidly retrieved and refilled after they have released neurotransmitters through a fusion pore. The molecular mechanism for this so-called 'kiss-and-run' mode of retrieval is essentially unknown. 4- 'kiss-and-stay' mode might be used, and this has been proposed for the rapid reuse of SVs. In this case, SVs never leave the active-zone membrane, but are refilled instantly after closure of the fusion pore. Sunday, September 19, 2010 Clathrin - Clathrin assembles acts to stabilize the curvature introduced into the growing pit while increasing its deformation until the entire region invaginates to form a closed vesicle. - The unassembled cytosolic form of clathrin is comprised of three molecules of heavy-chain and three molecules of light chain and is called a triskelion - As triskelions assemble, they tend to form closed cages with striking pentagonal and hexagonal faces. Sunday, September 19, 2010 Sunday, September 19, 2010 ...
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This note was uploaded on 09/21/2010 for the course NACS 641 taught by Professor Areneda during the Fall '10 term at University of Maryland Baltimore.

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