SLE1/MODULE 3- Synaptic Transmission Flashcards
what is sodium’s equilibrium potential
typically around +55 mV
synapse
before AP initiates + propagates, a cell receives current inputs to change the membrane potential (Vm)
what occurs at a synapse
a specialized connection enabling a change in membrane potential (Vm) in one cell to be transmitted to another
-presynaptic cell -> postsynaptic cell
2 types of neurons
-presynaptic
-postsynaptic
2 types of synapses
-electrical
-chemical
electrical synapse
direct transmission of current between 2 cells (presynaptic + postsynaptic)
chemical synapse
release of chemical agent by presynaptic cell to attach to postsynaptic cell, eliciting a change in membrane potential (Vm)
myelin
allows for movement of current for charges to be FASTER
what creates myelin
glial cells
what glial cells create myelin in CNS
oligodendrocytes
what glial cells create myelin in PNS
Schwann cells
what does speed of AP propagation depend on
whether or not there is myelin
-whether or not there is more myelin
-fewer nodes
-etc.
an AP will propagate quicker if there is myelin or nodes
myelin
when there is myelin, what happens
appears that AP is jumping from one node to another
-saltatory conduction
how do nodes make AP faster
there is a greater density of voltage gated sodium channels, allowing for greater depolarization
-more channels/conductors = ions can move through doorways quicker + have more effective impact
where are APs generated
axon hillock
describe AP generation
APs are generated at the axon hillock when there is enough depolarization ->
AP will propagate downwards towards node 1 ->
if there is enough sodium that influxes to depolarize, the AP will propagate to node 2 ->
same thing to node 3
why are APs generated at the axon hillock
it is the first place that membrane potentials accumulate
-this is where it is determined if an AP is going to occur or not
what makes the axon hiloock special
HAS HIGHEST DENSITY OF SODIUM CHANNELS
where are the most sodium channels found
axon hillock
gap junction
little separators between the presynaptic + postsynaptic neuron
another name for gap junctions
electrical synapses
what do gap junctions (electrical synapses) allow for
-high conductance/passage
-high capacity for electrical current to flow in either direction
describe gap junction role in AP generation
-voltage gated ion channels in presynaptic cell will generate electrical current, which will pass through the gap junction; WE MUST DO THIS FOR AN AP TO START
-if there are enough gap junctions, you will be able to get more current through from the presynaptic to postsynaptic neuron + you will get AP generation
what do gap junctions do
MOVE CURRENT/ MOVE CHARGES
why are gap junctions referred to as electrical synapses?
because they are conducting electricity
what do gap junctions conduct
charges, charged ions
cell-to-cell adhesions are also called
membrane junctions
cell-to-cell adhesions (membrane junctions)
use plasma membrane to put things near each other (only those cells that want to be tightly packed)
3 types of cell-to-cell adhesions (membrane junctions)
-tight junctions
-desmosomes
-gap junctions
tight junctions
serve to seal adjacent cells together so that fluids cannot leak between them (fluid barrier)
desmosomes
anchor adjacent cells together to resist pulling forces (anchoring junctions)
gap junctions
provide a “tunnel” between adjacent cells allowing direct electrical + metabolic coupling of the cells
metabolic coupling
capillaries, tiny blood vessels that don’t contact all the cells of the body so all the cells can’t get nutrients in discrete ways SO you need gap junctions for tissue like skin like avascular tissue to get rid of waste + get nutrients in
where are gap junctions found
many places throughout the body
intercellular communciation
cell-to-cell interaction is necessary for homeostasis
direct intercellular communication
gap junctions
indirect intercellular communication
chemical messengers used
-chemical messenger is released by 1 cell
-receptors on different (target) cell
indirect/direct communication always take more time/effort
indirect
-think about communicating with a friend through another person; takes more time/effort
-direct method is much faster
gap junctions
comprise pair of channels in the membranes of the presynaptic + postsynaptic cells
-direct electrical coupling between 2 cells
are gap junctions small/large
large enough to permit passage of ions contribution to membrane potential
gap junctions are fast/slow
very rapid
gap junctions are passive/active
passive
-signal can degenerate
-if I travel from node 1 to node 3, there is a possibility that the signal is no longer strong enough + the AP dissipates
gap junctions are unidirectional/bidirectional
bidirectional
-can go one way or another
-CANNOT go backwards until refractory period ends
gap junctions are depolarizing/hyperpolarizing
either
neurotransmitters are slow/fast
relatively slow
-0.5 ms
neurotransmitters are the primary synapse in what
human movement
what do neurotransmitters attach to
ligand or voltage gated receptors/channels
where are neurotransmitters storeed
in synaptic vesicles
where are neurotransmitters removed
in the synaptic cleft
2 types of neurotransmitters
-small-molecule transmitters
-neuroactive peptides (short polymers of amino acids)
what are neurotransmitters influenced by
-concentration
-types of ions along membrane
what do ions flow through
postsynaptic channels
what is determined by binding at the postsynaptic cell
whether the impact is excitatory/inhibitory
how far apart are presynaptic + postsynaptic neuron membranes
20-40 nm
AP steps
AP from presynaptic cell travels to end bulb ->
calcium enters ->
due to the influx of calcium, vesicles fuse to the presynaptic membrane + exit into the presynaptic cleft ->
vesicles release neurotransmitters into synaptic cleft ->
neurotransmitters attach to specific receptors + open them to allow ions to move to the postsynaptic neuron ->
the influx of ions changes the postsynaptic neuron membrane potential + generates an AP
more summarized AP steps
AP in presynaptic cell ->
release of neurotransmitters stored in vesicles of presynaptic terminals ->
ligand-gated channels receive neurotransmitter in postsynaptic cell, opening ion channels ->
change in cell memrbane potential postsynaptically
what do specialized channels allow for
influx of calcium when needed
-needed to communicate/move charged particles
how can we identify a neuromuscular junction
-there will be many labels for ACh
-motor end plate
ACh
neurotransmitter at the neuromuscular junction at the last synapse before we get to muscle contraction
motor end plate
postsynaptic terminal at the neuromuscular junction
what releases ACh
terminal button (the swellings formed by several branches at the axon)
ACh impact
significant impact on changes in the membrane potential at the muscle + results in muscle contraction/reduction in muscle contraction
what is found in the folds of the membrane
high density of ACh receptors
-ACh will be released but degrade VERY QUICKLY
why does degradation of ACh occur after release
due to enzymatic hydrolysis by acetylcholinesterase
acetylcholinesterase
an enzyme that causes rapid hydrolysis of ACh
-responsible for stopping the excitation of the nerve after the transmission of an AP
-diffuses across end plate receptors
**what is the neurotransmitter that is key to creating an AP at the neuromuscular junction
ACh
motor neuron
the neuron that connects the spinal cord to the neuromuscular system
steps in neuromuscular transmission/propagation
arrival of AP in motor neuron ->
opening of voltage gated Ca2+ channels, causing influx of Ca2+ ->
exocytosis of ACh, transfer + fusion vesicles containing ACh to presynaptic terminal ->
release of ACh in synaptic cleft + binding to receptors on ion channels ->
ion channels open ->
influx of Na+ and efflux of K+ causing depolarization of the membrane potential ->
generate AP
when does neuromuscular transmission stop
when ACh is removed from synaptic cleft
2 ways that ACh is removed from synaptic cleft
-ACh diffuses away from synapse
-ACh is broken down by enzyme acetylcholinesterase into acetic acid + choline
3 types of impairments
-receptor blockers
-degradation prevention
-diseases of neuromuscular junction
impairments- receptor blockers
receptor antagonist blocks ACh receptor
impairments- degradation prevention
-anticholinesterase drugs prevent the breakdown of ACh
-used to paralyze muscle during surgical procedures
impairments- diseases of the neuromuscular junction
-genetic transmission
-poor ACh packaging
-receptor impairments
-ACh enzyme mismanagement
Lambert-eaten myosthenic syndrome
immune disorder that influences neuromuscular junction
-destroys voltage gated calcium channels
myasthenias
involve weakness of musculature
-weakness varies day to day, as well as throughout the day
-there are experimental set ups you can implement to determine whether someone has 1 myasthenia syndrome vs another
which prominent syndrome results from myasthenia gravis, a disorder in which ACh receptors are targeted by the immune system, resulting in fewer ACh receptors
you will still be able to produce force, BUT LESS
-primary weakness of musculature occurs
where is first affected in myasthenia gravis
ocular/eye muscle weakness first
-then moves to muscles that affect swallowing, talking, chewing, etc.
how can myosthenia gravis be detected
through antibiodies through ACh receptors in the plasma
botox
bacterium clostridium botulinum
-potent neurotoxin that disrupts transmission as a chemical synapse
how does botox work
one part of the protein disables fusion proteins at the NMJ
how is botox administered
by injection into a muscle where it is transported by endocytosis into presynaptic terminals
paralysis via botox depends on what
dose
when does botox paralysis peak
at 5-8 days after the injection
how long does botox paralysis last
3 months
effects of botox
the disable of fusion proteins is permanent + causes some atrophy + demyelination of the axon
after botox, what does initial recovery of muscle function require
requires axon to develop sprouts + establish new synaptic contacts
what can repeated botox injections cause
can cause NMJs to become abnormal
can botox be transported retrogradely
yes- can be transported retrogradely back to the motor neuron + disrupts the function of central synapses
protocol for botox for wrinkles
injections into muscles every 3-6 months
medical uses for botox
-migraines
-back pain
-stuttering
-carpal tunnel syndrome
-overactive bladder
-multiple sclerosis
-cerebral palsy (spasticity)
-excessive sweating
-cervical dystonia
botox- what doesn’t work + what happens as a result
fusion proteins (proteins allowing vesicles with ACh to exocytose) do not work, so no ACh is release
-this is ultimately the thing that causes the muscle cell to not contract/have a reduction in contraction
if there is not an adequate amount of botox what would happen
reduction in muscle contraction
EPSP
excitatory post synaptic potentials
IPSP
inhibitory post synaptic potentials
synaptic integration
neurons receive currents that produce responses that can be excitatory/inhibitory postsynaptic potentials (EPSP or IPSP)
what does the amplitude of net excitatory PSP depend on
the sum of inputs (summation)
-if i have a bunch of excitatory coming in but also a bunch of inhibitory, I will have a net that is less than the big excitatory signal
2 types of summation
-spatial
-temporal
spatial summation
signal comes from multiple synapses or locations
types of spatial synapses
-axodendritic synapse
-axosomatic synapse
-axoaxonic synapse
axodendritic synapse
axon of presynaptic neuron connects to dendrite of postsynaptic neuron
axosomatic synapse
axon of presynaptic neuron latches to cell body/soma of postsynaptic neuron
axoaxonic synapse
axon of presynaptic neuron connects to axon of postsynaptic neuron
*see slides 30 + 31 image of types of spatial synapses
temporal summation
synapses come in a QUICK SUCCESSION from the SAME neuron
where does a neuron receive inputs
at the dendrites
where is AP generated
at axon hillock
where is AP transmitted along
along the axon to the target cells
where do most synapses that deliver info to the neuron occur
at the dendrites
-many of them on dendritic spines (the little knobs coming off of the dendrites)
dendrites
branches coming out of the soma/cell body
neuromodulation
the signals we get can be modulated
-summation is a way of modulating signals
what do neuromodulatory receptors do
increase responses that are evoked/caused by synaptic transmission
-these changes affect the ion channels + even change the things that happen afterwards with the postsynaptic receptor
2 types of neuromodulation
-presynaptic inhibition
-presynaptic facilitation
imagine there is a postsynaptic membrane with a bunch of receptors. if ions bind to modify/neuromodulate, what happens afterwards…
everything that happens afterwards is through SECOND MESSENGERS
-a bunch of things can affect how much or if at all the second messengers at the end of the postsynaptic terminal actually make things happen
presynaptic inhibition
occurs as an axon makes synaptic contact with another axon
-reduces amount of transmitter (CALCIUM) released by a presynaptic cell in response to an AP
what is a blip that doesn’t hit threshold called
EPSP
presynaptic facilitation
augment the influx of calcium into the presynaptic terminal + prolong the postsynaptic potential
-augment the influx of calcium into the presynaptic terminal + prolong the postsynaptic potential
what color do we typically color INHIBITORY neurons
black
what color for excitatory
beige
movement along an axon can be ____
bidirectional
axonal transport system
there are proteins (microtubules + other fibular elements) that regulate the stability + orientation of the cytoskeleton of the neuron
axonal transport along the cytoskeleton occurs in what directions
bidirectional
-both directions, forwards + backwards (anterograde/orthograde or retrograde)
anterograde/orthograde
movement of signals away from the soma
anterograde/orthograde axonal transport is driven by which enzyme
kinesin enzyme
retrograde
movement of the signals back toward the soma
retrograde axonal transport is driven by which enzyme
cytoplasmic dynein enzyme (molecular motor)
if a signal is coming in externally (Artificial stimualtion), you can have signals going in which directions
both ways from the location of the input
-BIDIRECTIONAL
if the signal is coming internally (ex: AP created because sent a voluntary signal from brain downstream)…what will occur
there will be a refractory period
-CANNOT HAVE A SIGNAL RETROGRADE AS WE ARE GOING ANTEROGRADE/ORTHOGRADE
what can axonal transport impact
the properties of nerve + muscle cell
(neurogenic or myogenic)
neurogenic
axonal transport from nerve to muscle
-ex: a nerve is cut
-impacts nervous system + muscular system, requires neurogenic factors to regulate normal properties of nerve-muscle system
myogenic
axonal transport from muscle to nerve
