Block 2 - Synapse 1-3 Flashcards
What is a synapse?
a region where communication occurs between two neurons or between a neuron and a target cell
How is a gap junction formed?
- proteins called connexins (six connexins assemble to form a hemichannel, or connexon)
- hemichannels on neighboring cells align with each other to create a pathway between the two cells
How does an electrical synapse function?
- gap junctions conduct electricity between two cells
- change in voltage in one cell spreads to the adjoining cell
- the gap between cells is smaller than a chemical synapse (3-4 nm)
- very fast bidirectional communication
- activity in the second cell is less than the first (no gain or amplification)
Electrical coupling allows —– to synchronize with one another
neurons
Gap junctions allow the myocardium to…
coordinate cardiac action potentials (contract all at the same time)
How does a chemical synapse function?
- presynaptic neuron secretes a chemical neurotransmitter into the cleft between the cells (about 20-25 nm)
- the chemical selectively activates receptors on the postsynaptic cell surface
- receptor activation causes a change in the postsynaptic cell (stimulation or inhibition)
- communication only occurs in one direction
What is the difference in the space between cells with electrical and chemical synapses?
electrical: 3-4 nm
chemical: 20-25 nm
In general, what is the process of creating/releasing a neurotransmitter across the synaptic cleft?
- synthesize the neurotransmitter
- package neurotransmitters into vesicles
- store the vesicles near the synaptic cleft
- release the transmitter on cue (voltage change) by fusing vesicles with the plasma membrane
- recapture the neurotransmitter from the synaptic cleft
- recycle and reuse vesicles lipids and proteins
What are the “jobs” of the presynaptic and postsynaptic cells?
presynaptic: make and package neurotransmitter, release neurotransmitter
postsynaptic: make and display receptors, respond to neurotransmitter
Describe the process of neurotransmitter release and response across the synaptic cleft
- membrane potential depol. in the presynaptic cell (possibly due to an action potential)
- fusion of neurotransmitter (NT) containing vesicles and emptying into the synaptic cleft
- diffusion of NT and binding to postsynaptic receptors
- change in open/closed state of ion channels in the postsynaptic cell membrane
- change in ion permeability of the postsynaptic cell membrane
- change in membrane potential in the postsynaptic cell
- response may be excitatory or inhibitory depending on receptor and ion channel characteristics
What are the two ways for excitation to occur in the postsynaptic cell?
- increasing Na+ channel conductance
- decreasing K+ channel conductance
What is a way that inhibition can occur in the postsynaptic cell?
- increasing K+ channel conductance
If Pk increases, what happens to the cell?
cell hyperpolarizes
If P Na increases, what happens to the cell?
cell depolarizes
How does the concentration of neurotransmitters in the synaptic cleft affect the actions of the cells?
increase concentration raises the probability of neurotransmitter molecules binding to receptors on the postsynaptic cell
At the neuromuscular junction, synapses relay signals from —– cells to —— cells
neuron cells to muscle cells
Describe the basic synapse steps of the neuromuscular junction
- nerve action potential opens voltage-gated channels on the presynaptic cell
- ACh vesicles fuse and ACh enters the cleft
- ligand (ACh) opens ligand-gated channels on the postsynaptic cell
- ion channels open and create a muscle action potential
- eventually acetylcholine esterase binds to the ACh and removes it from the ligand activated channels, which close upon dissociation
A channel receptor is —— while a seven helix receptor is ——
channel: ionotropic
seven-helix: metabotropic
True or False: Neurotransmitters only activate one type of receptor
False (some activate more than one type)
What is the difference between ionotropic and metabotropic receptors?
ionotropic: contains a neurotransmitter binding site and an ion channel
metabotropic: contains a neurotransmitter binding site coupled to a G protein that can relay signal to a separate ion channel
Response of the postsynaptic cell depends on…
receptor type (but more than one receptor may be present)
Fast axonal transport carries things in the —— direction toward the ——-
anterograde, toward the synaptic terminal/synaptic cleft
Describe the 6 steps of synaptic vesicle biogenesis
- delivery of synaptic vesicle components to the plasma membrane from the golgi/ER
OR… - endocytosis of synaptic vesicle components to form a new synaptic vesicle
OR… - endocytosis of synaptic vesicle components and delivery to endosome which will form the new vesicle
- budding of the synaptic vesicle from the endosome
- loading of the neurotransmitter into the synaptic vesicle
- secretion of the neurotransmitter by exocytosis in response to an action potential
Describe vesicle formation for the neurotransmitter glutamate
- enzyme PAG converts glutamine to glutamate
- vesicular glutamate transporters (vGLUTs) accumulate glutamate in vesicles byusing a proton gradient (acidici interior)
- vesicles are acidic because of the vesicular H+-ATPase pumps (or V-ATPase pumps)
Before vesicles are filled with neurotransmitters, they are full of…
protons
How do vesicles fill with a neurotransmitter?
exchange transporters use the high proton gradient (established by V-ATPase) as a driving force to move the neurotransmitter in and the protons out
Directly after a voltage reaches the synapse, what happens?
- voltage gated calcium channels open (by depolarization)
Vesicle fusion and release is (very/not very) selective and is guided by ——- that ——–.
highly selective
guided by SNARES that attach and tether the vesicle at the synapse active zone
(V snare, or vesicle snare, is grabbed onto by the T snare, or target snare to pull the vesicle to the membrane where it fuses and releases its contents)
True or False: A neuron only forms a synapse with one cell
False - a neuron can form synapses with many other cells
True or False: A postsynaptic neuron can only receive input from a single presynaptic neuron
False - several presynaptic neurons can converge by synapsing onto one postsynaptic neuron
To recycle glutamate, it is taken back up via…
EAATs (excitatory amino acid transporters)
After glutamate is released from vesicles (and the glutamate is done being used), what happens to the vesicles and the glutamate?
vesicles are recycled, glutamate is recaptured by the presynaptic cell and nearby glial cells via EAATs
How do EAATs work?
using the sodium electrochemical gradient, the EAAT shifts glutamate anions into the cell (Na+ and Glu shift into the cell together)
also, H+ move in and K+ move out
What is the difference between what shifts glutamate into vesicles and what shifts glutamate back into the presynaptic cell?
EAATs - shift glutamate back into the presynaptic cells after it dissociates from receptors
vGLUTs - shift glutamate into presynaptic vesicles for release into the synapse
What do glial cells for the synapse function?
help with neurotransmitter reuptake (move Glutamate and Na+ in while K+ moves out)
How does the ligand dissociate in a cholinergic synapse?
an enzyme, acetylcholinesterase (AChE), breaks down the neurotransmitter ACh, then choline is transported back into the axon terminal and used to make more ACh
What is Novichok?
a nerve agent that inhibits acetylcholinesterase (ACh does not break down)
What are the two types of postsynaptic receptors?
ionotropic - the receptor is an ion channel (ligand gated channel)
metabotropic - indirectly coupled receptor, the receptor and channel are separate structures which require a second messenger, the ligand that binds is the first messenger
Ionotropic glutamate receptors have ————— that affect ligand binding affinity, receptor physiology, modulation, and trafficking.
several asparagines that are N-linked glycosylation sites
If a cell has ionotropic glutamate receptors, what happens when glutamate concentration increases in the synaptic cleft?
more sodium channels are open, the cell depolarizes, and the signal relayed onward is excitatory
True or False: ionotropic receptor responses ALWAYS involve an ion channel opening
True - the receptor IS the channel
True or False: ionotropic receptor reponses ALWAYS cause depolarization of the postsynaptic cell
False - depending on which ions pass through the channel, the postsynaptic cell can depolarize (excitation) or hyperpolarization (inhibition)
If a cell has metabotropic glutamate receptors, what happens when glutamate concentration increases in the synaptic cleft?
In mGluRs (or GPCRs)…
- Glutamate binding causes GTP to exchange for GDP on the G-protein, and the alpha subunit dissociates to activate signaling pathways in the postsynaptic cell.
- Different mGluRs have different effects. The postsynaptic response may involve channels that either cause depolarization or hyperpolarization
What are two examples of second messengers used in GPCR signaling of metabotropic receptors?
protein phosphorylation or Ca++ release
Integral membrane proteins are made in the…
rough ER
Describe the characteristics of a graded potential
- occur in dendrites and cell body
- size varies with strength of stim.
- summative (additional stimuli add to the strength)
Changing the amount of vGLUT is linked to changes in…
protein synthesis and axonal transport
Changing the activity of vGLUt is linked to changes in…
H+ATPase, signaling pathways, and metabolism
The selectivity of communication between cells at a synapse depends on —– and —–.
which neurotransmitter and which receptors
True or False: only a specific neurotransmitter can activate a receptor’s mcehanism
False - receptor selectivity is not absolute, certain other molecules also have the ability to activate the mechanism
(for example, many drugs and alcohol can alter the activity of NMDA receptors)
Besides activity in the synapse itself, what else can effect the synapse?
intracellular messengers and their receptors (for example, endocannabinoids in THC/marijuana that activate CB1 receptors)
Terminating the synaptic response requires…
neurotransmitter uptake
What blocks serotonin reuptake?
SSRIs (used for depression, etc. by keeping serotonin in the synapse and on receptors longer)
What does cocaine do regarding the synapse?
blocks the uptake of dopamine/norepinepherine/serotonin causing them to accumulate in the synapse where it contains stimulating the receiver cell
What do amphetamines do regarding the synapse?
stimulate excess release of dopamine, overwhelming the processes of reuptake and enzyme breakdown
What do cigarettes do regarding the synapse?
nicotine stimulates the release of dopamine, stimulates one type of acetylcholine receptor known as the nicotinic receptor, while another substance in cigarette smoke blocks the MAO enzyme that catalyzes dopamine breakdown
What does methylphenidate (Ritalin) do regarding the synapse?
block the uptake of dopamine but in a more gradual and more controlled rate
What does ecstasy do regarding the synapse?
increase the release of dopamine at low doses that account for its stimulant properties
increases the release of serotonin at higher doses accounting for hallucinogenic properties
What does THC do regarding the synapse?
attaches to cannabinoid receptors throughout the brain but especially the cerebral cortex, cerebellum, basal ganglia, and hippocampus
Besides THC, what else attaches to CB receptors?
anandamide and endocannabinoids produced by the body
What do endorphins do regarding the synapse?
inhibit the release of the neurotransmitter GABA, which normally puts the brakes on dopamine release
endorphins also attach to the same receptors as opiates
Opioid receptors are one type of…
metabotropic receptors (GPCRs)
What do opiates do?
decrease sensitivity to pain and increase relaxation (morphine, heroin, and methadone)
Generally, how do exogenous opioids alter the reward pathways?
inhibit the inhibitory neurons, therefore increasing stimulation of dopamine release ad more “reward”
What are the three monoamines involved in the interdependent neurotransmitter system of mood? What does each control?
norepinephrine - stress response, fight or flight, circadian rhythms, energy, and arousal
dopamine - pleasure, reward, attention, and reinforcement
serotonin - appetite, social rank, well being, and sleep
How does the body adapt to opioid use?
with continued use, the system responds by desensitization or reducing the number of opioid receptor sites
causes a routine user to take more to produce the same effect, addicts are at high risk for overdose when they start using again after abstinence, and explains why users start drugs to feel high but end up needing them to not feel low
Cells diminish responsiveness to prevent…
3 methods are…
prevent overstimulation
receptor sequestration, receptor down-regulation, receptor inactivation
What are opioid receptor antagonists? How do they work?
Naltrexone HCl and Naloxone HCl
they have a higher binding affinity to opioid receptors, so they block opioids from binding allowing the person to breathe again and reverse the overdose
How does opioid overdose occur?
too much of an opioid binds to the receptors, slowing and eventually stopping the breathing
