2. Synaptic Transmission and Neurotransmitters Flashcards
electrical synapse
2 neurons are connected by a gap junction which allows electrical current to flow directly from one cell to another
connexin
located on pre and post synaptic clefts with very small gap between
size of electrical synapse gap
3nm
gap junction
aggregates of intercellular channels that permit direct cell–cell transfer of ions and small molecules
types of ions/molecules that can pass through gap junction
Ca2+
IP3
cAMP
Na+
etc
Charcot-Marie-Tooth disease
affects sensory and motor nerves in arms, hands, legs, feet.
nerves degenerate and lose ability to communication with distant targets
Action Potential in CMT disease
decreased
CMT disease type
heterogenous genetic disease
CMTX1
2nd most common form of CMT
caused by x-linked mutations in a gene that provides instructions for making the protein connexin-32
connexin-32 is part of gap junction channels in myelinating schwann cells
chemical synapses
release neurotransmitters from presynaptic membrane and bind to its receptors on postsynaptic or presynaptic membrane
chemical synapse gap distance
30nm
where are VG Ca++ channels located?
presynaptic membrane
parts of a neural synapse
presynaptic terminal
postynaptic terminal
synapse
vesicle
neurotransmitters
receptors
quantal release
the release of neurotransmitters in a vesicle into the post synaptic cleft
large amt released per vesicle
quantal release triggers
either an IPSP or EPSP in the postsynaptic membrane
SNARE proteins
protines in the synaptic vesicle and presynaptic membrane that help dock the vesicles and zip together to force the membranes to fuse
what happens if SNARE proteins are destroyed/cleaved?
nuerotransmitters cannot be release from the synaptic vesicles
botulinum toxin
cleaves SNARE proteins preventing the release of NTs
where are small molecule NTs made?
terminal
where are peptides made?
cell body
Cholinergic
release Ach
Dopaminergic
release dopamine
noradrenergic
release norepiniphrine
glutamatergic
release glutamateG
GABAergic
release GABA
peptidergic
release Peptide
1 neuron can connect with _____other neurons
over 1000
axon terminals can synapse with any part of target neurons
- dendrite
- cell bodies
- axon
motor unit
1 motor neuron and the muscle fibers it innervates
neurons in the brains use
60% Glutamate
30% GABA
NTs released by hypothalamus
- thyrotropin-releasing hromone (TRH)
- luteinizing hormone releaseing hormone (LHRH)
- somatostatin
NTs released by pituitary
-adrenocorticotropic hormone (ACTH)
-prolactin
-luteinising hormone
-thyrotropin
-growth hormone
-vasopressin
-oxytocin
endorphine NTs
enkaphalins
opioids
other NTs
substance P
bradykinin
angiotensin II
Endocannabinoids (eCBs)
Mechanism
- produced at postsynaptic neuron
- flow back to presynaptic where it will bind to CB1 receptor, inhibiting Ca++
- decrease NT release
GABA w/out eCBs
GABA released from the presynaptic will inhibit postsynaptic NT release
decrease dopamine release (NT) release
***need to review slide 18
GABA w/ eCBs
eCBs produced in postsynaptic neuron flow back to presynaptic CB1R
binding to CB1R inhibits Ca++ channels, decreasing GABA release.
Decreased GABA release will increase dopamine (NT) release
Glutamate
Excitatory
Glutamate NT release from presynaptic will increase NT release from postsynaptic.
If eCBs present in postsynaptic, eCBs will bind to presynaptic CB1R, inhibiting Ca++ channels, decreasing Glutamate NT release. A decreased Glutamate release will decrease the postsynaptic NT release.
Neurotransmitter receptor types
- ligan-gated ion channels
- g-protein coupled receptors
- enzyme linked receptors
ligand-gated ion channels
ionotropic receptors
ion chanels
G-protein coupled receptros
metabotropic receptors
GABA Receptor
ligand-gated ion channel
GABA binds to receptor
ion channel opens
Cl- rushes into cell
hyperpolarization
(IPSP)
agonist
chemical that activates a receptor to produce a biological response
antagonist
A chemical substance that binds to and blocks the activation of certain receptors on cells, preventing a biological response.
Isoflurane and GABA
isoflurane is a GABA agonist
facilitates ion channel opening and Cl- influx
Propofol and GABA
propofol decreases the rate of dissociation of GABA from receptor
increase duration of GABA activated opening of Cl- channel
more Cl- influx
hyperpolarization (IPSP)
ethanol and GABA
mimics GABAs effect on the braing by binding to GABA receptors and inhibiting neuronal signaling
IPSP and EPSP
IPSP: binding triggers Cl- influx
EPSP: mechanism unknown
metabotropic receptors
activated G-protein diffuses in the membrane to act on its target, which may be an ion channel, enzymes, or gene transcription.
Types of Ach receptors
ionotropic
metabotropic
ionotropic Ach
nicotinic Ach receptor
skeletal muscle
brain
nerves
metabotropic Ach
muscarinic Ach receptor
brain
peripheral organs
ways to stop NT action
- reuptake
- breakdown
- diffusion
reuptake
NTs can be returned to axon terminals for reuse or transported into glial cells
breakdown
enzymes inactivate neurotransmitters
AchEsterase (AchE)
diffusion (NT)
NTs can diffuse out of the synaptic cleft
lidocaine
VG Na+ channel blocker
AP cannot be generated
tetrodotoxin
VG Na+ channel blocker
depolarization inhibited
botulinum toxin
cleaves SNARE proteins
decrease NT Ach release
nerve gas
binds to AChE and disables AChE
increases ACh levels in synaptic cleft, triggers long lasting muscle contraction
Curare
competitively bind to nAChR
less Ach can bind to receptor
less EpP generated
less AP generated
weakness in skeletal muscles
MDMA
increases release of and binds to dopamine and 5-HT transporter
Cocaine
binds to dopamine transporter
blocks dopamine uptake
increased dopamine in synaptic cleft
SSRIs
bind to 5-HT transporter
blocks seratonin uptake
increased seratonin in synaptic cleft
