kenyon neurotransmission 2 Flashcards
four types of receptors
channel linked receptors
enzyme linked
GPCR
intracellular receptors (for unconventional NTs)
ionotropic receptors also known as
ligand gated ion channels or channel linked receptors
ionotropic receptor structure
single transmembrane multimeric protein that binds to NT and is the channel
how do we get functional diversity in ionotropic receptors?
by mixing and matching subunits we can produce hundreds of types.
for each receptor, we can combine 4-5 different subunits for that particular receptor
metabotropic receptors aka
GPCR
metabotropic receptor fxn in terms of ion
-Binding of NT activates trimeric G-proteins; these G proteins directly and indirectly influence the opening and closing of ion channels
(along with a thousand other activities).
define orphan receptor
a 7-transmembrane protein that looks like a metabotropic receptor, but we dunno what is its ligand
muscarinic and dopamine and adrenergic,
glutamate and GABA,
histamine and serotonin, and purine receptors are part of what class?
metabotropic!!!!
metabotropic receptor functional diversity
DON’T MIX AND MATCH
but the respective G protein pathways are basically unlimited
ionic power of metabotropic receptor
EPSP or IPSP, not huge action potentials
ionic power of ionotropic receptors
- minor change of membrane potential
- but if Ca++ flows through, it can initiate an AP
ELR (enzyme linked receptor) mech
NT activates a tyrosine kinase that (1) directly or (2) indirectly opens or closes ion channels.
also does a bunch of other stuff
intracellular receptors are mainly for?
unconventional NTs
list the major small molecule NTs (4)
ACh
AAs(glutamate, aspartate, GABA, and glycine)
Biogenic amines (catecholamines, sertonin, and histamine)
Purines (ATP, ADP, and adenosine)
ACh locations
- neuromuscular junctions
- preganglionic autonomic ganglia
- post-ganglionic parasympathetic
- many CNS neurons
how does ACh get made?
@presynpatic terminal
acetyl coA + choline —–> acetylcholin
^^^key enzyme: choline acetyltransferase
how does ACh get deactivated?
happens in the synaptic cleft
gets inactivated by ACETYLCHOLINESTERASE
How does the choline get recovered?
Na+/choline antiporter on the presynaptic terminal
Nicotinic AChR (Nm and Nn) are what kind of receptors?
IONOTROPIC!!!!
How conserved are the Nm or Nn receptors?
Nm = VERY conserved
Nn = TONS of kinds (combine 4-5 subunits!)
muscle nAChR types of subunits
both Nm and Nn have the same three subunits
-alpha 1, alpha 1, beta 1
differ in the last two subunits
- fetal mammals and torpedo: gamma and delta
- adult mammals: delta and epsilon
things that bind to the a1 subunit on Nm
ACh, nicotine, curare, bungarotoxin
Neuronal NAChR structure
still pentamers
alpha subunits: 1-10
beta subtunits: 1-4
a7: are Ca++ channels
What does this mean?
lots of room for diverse pharmacology
targets for skeletal muscle nACh receptors
curare, d-tubocurarine, succinylcholine, and alpha bungarotoxin
targets for neuronal nACh receptors
hexamethonium
muscarinic AChR–ionotropic or metabotropic?
metabotropic, so they’re connected to G proteins that will eventually influence opening or closing ion channels
types of metabotropic AChR
M1-M5
found in many neurons, SM, and cardiac muscle!!!!
(definitely not part of normal neuromuscular transmission)
what’s the main fast excitatory NT in the nervous system?
GLUTAMATE
half of brain synapses are glutamatergic
glutamate recycling
-some of the glutamate is simple reuptaked directly into the presynaptic terminal. The rest has to go through EEAT
- the glutamate from the synaptic cleft diffuses into EEAT channels on glial cells
- in the glial cell, glutamine synthetase (KEY) converts glutamate to glutamine.
- this glutamine then leaves the glial cell through SN1 channel, and then enters through SAT2 channels on the presynaptic neuron
what passes through all the ionotropic glutamate receptors?
Cations!!!! all of them mediate EPSPs!
input slide
input slid
input slide
input slide
input slide
in
what passes through the pore of NMDA receptor?
Na+, K+, and Ca++..
@negative potentials, these receptors allow Na+ to come in
@positive potentials, K+ mostly goes out
@zero mV, the permeability of Na+ entering the cell is the same as the permeability of K+ leaving the cell!!!! so zero net permeability
what does Mg2++ do to NMDA receptors?
it blocks the channel if the membrane potential is negative (below zero or resting)
consequence: NMDA receptors alone can’t do ANYTHING at the resting potential
how can we pop the Mg++ out?
depolarization pops the Mg++ out of the NMDA channels.
how? neighboring AMPAs can depolarize the neuron, relieving the Mg++ block…. this eventually allows Ca++ to rush through the NMDA receptors
^great case of synpatic plasticity
that one slide on just the NMDA picture
wait for lecture
slides on NDMA GRAPH
wait
slide on NDMA GRAPH
WAIT
