Basic Neurochemistry

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

in presynaptic terminal
ex. choline taken in through membrane, form ACh, then put in vesicle

1) small molecule neurotransmitter
2) peptidergic neurotransmitter

empty vesicles pass through axon
* also have recycled vesicles
fuse to presynaptic membrane

standard amino acids or simple derivatives
*ACh is exception

vesicles produced and packaged in cell body
vesicles are bigger content and pass through axon

larger peptides within ER and Golgi

linear line of small bumps are vesicles
big dents are Ca2+ channels -> shows its stimulated

it is a K+ current block -> creates longer AP
number of quanta released directly proportional 4-AP and #vesicles forming

The higher the voltage the higher the influx of calcium
Eca around +60 -> as approach +25 mV -> influx flattens out

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 said- neuron continuous electrical network
RYC said- neurons separate cells
both right G -gap junctions like in cardiac/ RYC – chemical

measured time from peak of AP to 2/3 of peak

determined by passive electrical properties of dendrites

vesicles with transmitter + ca dependent release + binding to receptor -> postsynaptic potentials in dendritic or somatic membranes

do differ from stronger presynaptic inputs

most are subthreshold and need multiple to surpass threshold and produce action potential

generally ionotropic transmission

generally metabotropic transmission

receptors

receptors form an ion channel pore = ligand-gated

receptors are indirectly linked with ion channels on the plasma membrane of the cell through signal transduction mechanisms, often G proteins.

stronger signal in centrally located synapse, distal signal diffused more

1) postsynaptic receptor
2) presynaptic receptor (autoreceptor)
3) presynaptic receptor (heteroreceptor)

located on soma, dendrite, or dendritic spine of postsynaptic cell

transmitter being released by axon has receptors for transmitter located on same presynaptic terminal
usually negative autoregulation

axo-axonic receptor (probably inhibitory) on presynapse from a transmitter from other axon

subunits with ion channel and receptors
ion channel part of receptor

7 transmembrane domains
1 or 2 subunit receptor
coupled to heterotrimeric G proteins (GDP/GTP)

binds GDP/GTP

unbounded by transmitter, alpha bound to ADP

G protein bound to neurotransmitter -> GTP + separation of alpha subunit
this catalyzes reaction of effector

Neurotransmitter leaves and goes back to GDP basal state

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

only indirectly, opposite of ionotropic receptors which receptor is same protein that contains ion channel

Gs, Gi, Gq -> alter neuronal function mostly through activation of protein kinases

increase/decrease adenylyl cyclase to affect cAMP
coupled with dopamine receptor

PKA

phospholipase C -> precursor to diacylglycerol (DAG) and Inositol trisphosphate (IP3)
3rd messenger is calcium ions

DAG -> protein kinase C
IP3 -> rector on ER

Ca2+which then activates voltage gated channels

PKC
calmodulin
Ca/calmodulin dependent protein kinase

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

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

ion channels – modulate neuronal activity
enzymes – neurotransmitter synthesis
cytoskleton proteins – maintenance of neuronal structure
transcription factors – gene expression

receive neurotransmitter
D1,3,5 increase adenylyl cyclase
D2,4 decrease adenyly cyclase

alpha 1- increase phospholipase C
alpha 2- decrease adenylyl cylcase
beta – increase adenylyl cyclase

receive aceylcholine
increase Na/K+ conductance
increase phospholipase C
decrease adenylyl cyclase and G protein coupling

a = fast acting
b = K+/Ca conductance (G-p coupled)
c = cl- conductance

AMPA – Na/K conductance
NMDA – na, K, ca conductance
metabotropic-increase phospholipase C