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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
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
Sunday, September 19, 2010 Synaptic delay in chemical synapses
Diffusion of ACh in
synaptic cleft (50 nm)
Delay mostly due
to the NT release
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
Sunday, September 19, 2010 Slow
Adler et al. 1991 Quantal Release of NT The EPP is
quantal units that
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
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
Ca2+ channels open
NT released into
NT binds to receptor
– o pens channels
Ions enter 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
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
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.
- Fall '10