Basic Neurochemistry

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neurotransmitter characteristics
1) vesicle storage
2) Ca dependent release
3) interaction with postsynaptic target
*interaction with target should illicit uniform response
almost meets all of criteria of neurotransmitter but some discrepancy
have slow and long lasting effects
forming vesicle
in presynaptic terminal
ex. choline taken in through membrane, form ACh, then put in vesicle
2 main types of transmitter biosynthesis
1) small molecule neurotransmitter
2) peptidergic neurotransmitter
small molecule neurotransmitter
empty vesicles pass through axon
* also have recycled vesicles
fuse to presynaptic membrane
types of small neurotransmitter molecules
standard amino acids or simple derivatives
*ACh is exception
peptidergic neurotransmitter
vesicles produced and packaged in cell body
vesicles are bigger content and pass through axon
types of pedtidergic neurotransmitter
larger peptides within ER and Golgi
Freeze frame of frog NMJ EM
linear line of small bumps are vesicles
big dents are Ca2+ channels -> shows its stimulated
effect of 4-AP
it is a K+ current block -> creates longer AP
number of quanta released directly proportional 4-AP and #vesicles forming
relationship between presynaptic voltage and calcium influx
The higher the voltage the higher the influx of calcium
Eca around +60 -> as approach +25 mV -> influx flattens out
Otto Loewi exp
hearts connected by tube in solution
1 heart stimulated by vegas nerve -> stimulates other (both hearts slow down in experiment)
shows neurotransmitter pass through solution
*vegas uses neurotransmitter
Golgi and Ramon Y Cajal
golgi said- neuron continuous electrical network
RYC said- neurons separate cells
both right G -gap junctions like in cardiac/ RYC – chemical
decay time
measured time from peak of AP to 2/3 of peak
rate of decay
determined by passive electrical properties of dendrites
synaptic actions
vesicles with transmitter + ca dependent release + binding to receptor -> postsynaptic potentials in dendritic or somatic membranes
EPSP and IPSP amplitude
do differ from stronger presynaptic inputs
EPSP and threshold
most are subthreshold and need multiple to surpass threshold and produce action potential
generally ionotropic transmission
generally metabotropic transmission
determinant of speed
Ionotropic receptors
receptors form an ion channel pore = ligand-gated
metabotropic receptors
receptors are indirectly linked with ion channels on the plasma membrane of the cell through signal transduction mechanisms, often G proteins.
Synapse distal vs centrally located
stronger signal in centrally located synapse, distal signal diffused more
locations of neurotransmitters
1) postsynaptic receptor
2) presynaptic receptor (autoreceptor)
3) presynaptic receptor (heteroreceptor)
postsynaptic receptor
located on soma, dendrite, or dendritic spine of postsynaptic cell
presynaptic Autoreceptor
transmitter being released by axon has receptors for transmitter located on same presynaptic terminal
usually negative autoregulation
presynaptic heteroreceptor
axo-axonic receptor (probably inhibitory) on presynapse from a transmitter from other axon
Structure of ionotropic neurotransmission
subunits with ion channel and receptors
ion channel part of receptor
structure of G protein couple receptors (metabotropic)
7 transmembrane domains
1 or 2 subunit receptor
coupled to heterotrimeric G proteins (GDP/GTP)
G proteins
binds GDP/GTP
basal state
unbounded by transmitter, alpha bound to ADP
Activated state
G protein bound to neurotransmitter -> GTP + separation of alpha subunit
this catalyzes reaction of effector
Neurotransmitter leaves and goes back to GDP basal state
G proteins subtypes in brain (4 major)
Gs, Gi, Gq(p), Go
stimulating -> increase adenylyl cyclase
inhibiting -> decrease adenylyl cyclase
increase phopholipase C
directly coupled with ion channels
increase K+, Ca2+ channels
G protein effect on ion channels
only indirectly, opposite of ionotropic receptors which receptor is same protein that contains ion channel
second messengers
Gs, Gi, Gq -> alter neuronal function mostly through activation of protein kinases
2nd messenger of Gs, Gi
increase/decrease adenylyl cyclase to affect cAMP
coupled with dopamine receptor
target of cAMP
2nd messenger of Gq
phospholipase C -> precursor to diacylglycerol (DAG) and Inositol trisphosphate (IP3)
3rd messenger is calcium ions
target of DAG and IP3
DAG -> protein kinase C
IP3 -> rector on ER
2nd messenger of Go
Ca2+which then activates voltage gated channels
target of Ca2+
Ca/calmodulin dependent protein kinase
Cyclic nucleotide-gated channels
conducts K+, Na, Ca currents nonselectively when bound to cGMP and cAMP
belong to voltage gated family even tho gates are not very voltage dependent
used in retinal and olfactory neurons
cAMP activation of PKA
PKA (tetramer) binds with 4 molecules of cAMP
dissociation expose catalytic subunits to phosphorylate many types of proteins
4 Ca binding protein -> complex regulates multiple enzymes (CaMK)
calcium sensor for neurotransmitter release
binds calcium in chemical synapses
substrates of neuronal protein kinases
ion channels – modulate neuronal activity
enzymes – neurotransmitter synthesis
cytoskleton proteins – maintenance of neuronal structure
transcription factors – gene expression
Dopamine receptors
receive neurotransmitter
D1,3,5 increase adenylyl cyclase
D2,4 decrease adenyly cyclase
norepinephrine receptors
alpha 1- increase phospholipase C
alpha 2- decrease adenylyl cylcase
beta – increase adenylyl cyclase
nicotinic muscarinic
receive aceylcholine
increase Na/K+ conductance
increase phospholipase C
decrease adenylyl cyclase and G protein coupling
GABA a, b, c receptors
a = fast acting
b = K+/Ca conductance (G-p coupled)
c = cl- conductance
glutamate receptors
AMPA – Na/K conductance
NMDA – na, K, ca conductance
metabotropic-increase phospholipase C
Categories: Neurochemistry