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Printable Handouts
Navigable Slide Index
- Introduction
- Introduction to NMDA receptors
- Glutamatergic synapses
- Ionotropic glutamate receptors
- NMDAR subunit stoichiometry and subtypes
- NMDAR topology and agonist binding
- Calcium permeability of NMDARs
- Voltage-dependent NMDAR channel blockage
- Subtype dependence of functional properties
- NMDAR subtype expression in neurons
- Patch-clamp analysis of recombinant NMDARs
- Measuring Mg2+ IC50
- Vm dependence of Mg2+ IC50
- Slow deactivation kinetics
- Regulation of GluN2 subunit expression
- 2 groups of NMDAR subtype-dependent properties
- Gating and ligand-binding properties
- Modulation of NMDARs by the NTDs
- NTD dependence of NMDAR maximal P(open)
- NTD dependence of glutamate potency
- Many NMDAR properties controlled by the NTD
- Subtype dependence of channel properties
- Residues involved in subtype-dependent properties
- Control of inhibition by Mg2+
- Control by the GluN2 S/L site of Ca2+ selectivity
- Control of single-channel conductance
- Slow Mg2+ unblock and Vm-dependent gating
- Control by GluN2 S/L site of Vm-dependent gating
- Molecular coupling of GluN2 S/L site to channel
- Effects on Mg2+ inhibition of GluN2 S/L mutations
- Homology model based on bacterial NaK channel
- Homology model of GluN1/2A receptor channel
- Homology model prediction
- GluN2A(S632) – GluN1(W608) coupling
- Summary
- Acknowledgements
Topics Covered
- General structural and functional properties of NMDA receptors
- Divergent functional properties of NMDA receptor subtypes
- Two groups of NMDA receptor subtype-dependent properties can be defined both structurally and functionally
- Diversity of NMDA receptor gating and ligand-binding properties
- Diversity of NMDA receptors channel properties
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Talk Citation
Johnson, J. (2014, April 2). Molecular basis of NMDA receptor functional diversity [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 3, 2024, from https://doi.org/10.69645/OGYB2780.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Jon Johnson has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
A selection of talks on Biochemistry
Transcript
Please wait while the transcript is being prepared...
0:00
Hello, my name is Jon Johnson.
I'm a professor in the
Department of Neuroscience
at the University of Pittsburgh.
My talk concerns NMDA receptors,
a type of glutamate receptor
found in most fast
excitatory synapses
in vertebrate nervous systems.
I will describe some of the basic
characteristics and functions
of NMDA receptors, diversity
of NMDA receptor properties,
and the molecular basis for
NMDA receptor diversity.
0:26
I will start by introducing the
function, structure, and some
of the salient properties
of NMDA receptors.
0:33
NMDA receptors are found at
glutamatergic synapses, the most
common type of fast excitatory
synapse on vertebrate neurons.
Glutamate released from
the presynaptic terminal
of glutamatergic synapses binds to
and activates glutamate receptors
in the postsynaptic membrane.
Typically, there is a mix of
several types of glutamate receptors
including NMDA receptors in
the postsynaptic membrane
at each glutamatergic synapse.
NMDA receptors are ionotropic
glutamate receptors,
which are ligand-gated ion
channels that incorporate
both agonist binding
sites and an ion channel
into a single molecular complex.
All ionotropic glutamate receptors
are tetrameric proteins--
that is, proteins
composed of four subunits.
An ion channel is formed and
surrounded by the four subunits.
1:21
There are three types of
channel-forming ionotropic
glutamate receptors-- NMDA,
AMPA, and kainate receptors.
All three receptor types can be
found in the postsynaptic membrane
of glutamatergic synapses as well
as at other locations on neurons.
It is very common to
find NMDA and AMPA
receptors co-localized
postsynaptically.
The subunits that can contribute
to each type of glutamate receptor
are shown here.
The subunits that
form NMDA receptors
are divided into three groups.
A single gene encodes
the Glu in one subunit,
which exists as eight
splice variants.
There are four types
of Glu in two subunits
and two types of Glu
in three subunits,
each encoded by a separate gene.