Nuerotransmitters Flashcards
Describe whats happening in the image below- glutamate?
Give examples of the name of the receptors? NMDA or AMPA
Name the transporter?
State how the neurotransmittor is removed from the cleft and state what happens to it?
What happens when you have abnormal cell firing?
Glutamate is formed from intermediary metabolism (e.g. glycolysis and the Krebs’ cycle - it is formed from the transamination of alpha-ketoglutarate)
It interacts with the receptor and causes the entry of sodium and calcium through the NMDA receptor
Transporters on the pre-synaptic membrane and on glial cells causes the uptake of glutamate once it has fulfilled its role
The main transporter is EAAT2 (Excitatory Amino Acid Transporter 2) which is found on glial cells and on the pre-synaptic membrane
Once in glial cells or in the neurones, glutamate is then inactivated by glutamine synthetase to make glutamine (you simply add an amino acid onto the glutamate at it becomes inactivated)
Abnormal cell firing leads to seizures associated with excess glutamate in the synapse
State a neurotransmittor which is excitatory and inhibatory?
Sate why they are like that?
Na+- Excitatory- depolarisation
Cl- - Inhibatory- hyperpolarisation
What are complex partial seizures?
This term replaces complex partial seizures. … Theseseizures may have an aura (or warning, which technically is itself a focal aware seizure). Theseseizures include automatisms (such as lip smacking, picking at clothes, fumbling), becoming unaware of surroundings, and wandering.
How wide is the synaptic cleft?
20 - 100 nm wide
How does calcium effect AMPA receptors?
What is the mechanism of action for Tiagabine?
Inhibits GABA reuptake
Focal seizures with or without secondary generalisation
What is the mechanism of action for Vigabatrin?
Inhibits GABA transmainase
What are atonic seizures?
LOSS OF MUSCLE TONE
List 5 features of synaptic transmission?
Rapid timescale
Diversity
Adaptability
Plasticity
Learning and memory
What type of receptor is catagorised as slow>
Its effectors may be enzymes (adenyl cyclase, phospholipase C, cGMO-PDE) or Channels (Ca2+ and K+)
What is the mechanism of action for valproate?
Weak effect on GABA transaminase and on Na+ channels
Most types, especially absence seizures
What is neurotransmission action defined by?
Receptor Kinetics
List 4 vesicular neurotoxins and their mechanism of action?
What is excess glutamate in the synapse associated with?
Abnormal cell firing leads to seizures associated with excess GLUTAMATE in the synapse
What are dendritic spines?
Spines are neuronal protrusions, each of which receives input typically from one excitatory synapse. They contain neurotransmitter receptors, organelles, and signaling systems essential for synaptic function and plasticity.
Glutamic acid decarboxylase is dependant on what vitamen?
B6
Where is an action potential generated?
Axon hillock
What are abscence siezures?
An absence seizure causes you to blank out or stare into space for a few seconds. They can also be called petit mal seizures. Absence seizures are most common in children and typically don’t cause any long-term problems. … Absence seizures are a type of epilepsy, a condition that causes seizures.
Explain the process of docking?
There are a large number of protein in the axon terminal
Some vesicles are docked in the active zone at the site of the synapse
Other vesicles are floating in the terminal region
There is an interaction between the presynaptic membrane and the vesicle proteins allowing the vesicle to be docked stably
There are alpha helical structure which interact together to form a super helix
The net effect of this interaction is a stable complex of the vesicle at the synapse full of neurotransmitter
The vesicle needs a signal to be release and the signal is CALCIUM
At these sits of docking of the vesicles you find a high concentration of calcium channels
Calcium enters through the channel and causes a calcium dependent change in a calcium sensor protein on the vesicle making the complex undergo conformational change
This drives the release of transmitter into the synaptic cleft
How are neurotransmitters removed from the synaptic cleft?
What is the mechanism of action for Phenobarbital?
Enhanced GABA action and inhibition of synaptic excitation
Doesn’t work on absence seizures
List 4 types of generalised epilepsies ( seizures)?
Tonic- Clonic
Abscence
Myoclonic
Atonic
How many molecules are there per synaptic vesicle?
4,000-10,000 molecules per SV
Why is there a lot of mitachondria in the axon terminal?
There are lots of mitochondria in the axon terminal because energy is needed to release neurotransmitter
What can you do if you exploit the GABA receptors?
By exploiting the GABA receptor you can produce anti-epileptics, sedatives and muscle relaxants
There is a binding site for benzodiazepines (e.g. diazepam)
There is a binding site for barbiturates (used for treatment of epilepsy) - this alters the frequency of channel opening
Explain the inactivation process of GABA?
GABA is the main inhibitory neurotransmitter
GABA and glutamate have very similar structures - removal of carboxyl group in glutamate gives you GABA
GABA is synthesised by Glutamic Acid Decarboxylase (GAD) - this is a Vitamin B6 enzyme
GABA binds to the receptor and allows the entry of chloride which hyperpolarises the cell
There are transporters on Glial cells and on the presynaptic neurone which takes up GABA - these are GABA Transporters (GAT)
Once GABA has been taken up by the glial cell, it can be inactivated by an enzyme called GABA transaminase giving Succinate semialdehyde - this can feed into the TCA cycle
Which one of the Glutamate receptors are Fast excitory synapses and have a rapid onset, offset and desensitisation?
AMPA receptors
Ion channel lined receptors
What are tonic-clonic seizures?
A tonic-clonic seizure usually begins on both sides of the brain, but can start in one side and spread to the whole brain. A person loses consciousness, muscles stiffen, and jerking movements are seen. These types of seizures usually last 1 to 3 minutes and take longer for a person to recover.
List the two Glutamate receptors and state their features?
Coincidence transmission- in resting state it is inactive, it is only activated if their has been a previous input into the cell for example depolarisation through an AMPA receptor. And if it has been depolarised then this receptor is activated. You need to havet two events occuring in the cell
NMDA-
Slow component of excitatory mechanism
Needs TWO INPUTS for this receptor to become activated
The membrane needs to be depolarised AND the glutamate must bind
So NMDA activation is dependent on the state of depolarisation of the cell
This also lets in calcium
List 3 examples of partial epilepsies (seizures)?
Simple
Complex
Secondarily Generalised
What are the mechanism of action for benzodiazepines?
Enhanced GABA action
What glutamate receptor fits this description?
Slow component of excitatory transmission.
Serve as coincidence detectors which underlie learning mechanisms
NMDA receptor
How fast is synaptic transmission?
vFast ~ within ms (200 us)
What type of receptor mediates all fast excitatory and inhibatory transmission?
Ion channel receptor
Effects of the drugs in a diagram
What happens to the information propagated down the dendrites?
The information then propagates down the dendrite and integration occurs in the soma
What are partial siezures?
Focal seizures (also called partial seizures and localized seizures) are seizures which affect initially only one hemisphere of the brain.
List two examples of Ion channel receptors found in the CNS and 1 example found in the NMJ?
What are the steps for neurotransmission
Action potential comes along and the voltage gated calcium channel gets activated
Calcium enters the nerve terminal and you get exocytosis of the neurotransmitter
It diffuses across the gap and interacts with the receptors
How long does it take for one action potential to get from one cell to the next?
2 ms for the action potential to get from one cell to the next
What 3 things does transmitter release require?
What are generalised epilepsies (seizures) ?
Generalized seizures affect both cerebral hemispheres (sides of the brain) from the beginning of the seizure. They produce loss of consciousness, either briefly or for a longer period of time
What are secondary generalized seizures?
When a partial seizure spreads to the other side of the brain, it is known to “secondarily generalize.” Partial seizures that secondarily generalize may include convulsions or spasms, a loss of muscle tone, or a decrease in muscle tone.
List some examples of neurotransmitters for G-protein coupled receptors?
What is epilepsy treatment focused on?
Epilepsy treatment is focussed on damping down excitatory activity by facilitating inhibitory transmission
What are simple partial seizures?
Simple partial seizures are localized to one area on one side of the brain, but may spread from there. Consciousness is not lost during a simple partial seizure. The left side of the brain controls the right side of the body, and the right side of the brain controls the left side – so it can be relatively easy for a doctor to identify which side of the brain is being affected by a simple partial seizure.
Physicians typically break simple partial seizures down into four areas, depending on the location in the brain and parts of the body affected:
Motor – A simple partial seizure with motor symptoms will affect muscle activity, causing jerking movements of the foot, face, arm, or another part of the body. Physicians can diagnose which side of the brain is affected by observing which side of the body experiences symptoms (left brain controls right side, right brain controls left side).
Sensory – A simple partial seizure with sensory symptoms affect the senses: hearing problems, possible hallucinations, and other distortions.
Autonomic – A simple partial seizure with autonomic symptoms affects the part of the brain responsible for involuntary functions: it may cause changes in blood pressure, heart rhythm, bowel function, etc.
Psychic – A simple partial seizure with psychic symptoms affects parts of the brain that trigger emotions or previous experiences: it may cause feelings of fear, anxiety, déjà vu (the feeling that something has been experienced before), etc.
epilepsy
What are myoclonic seizures?
Myoclonic seizures are brief shock-like jerks of a muscle or group of muscles. They occur in a variety of epilepsysyndromes that have different characteristics. During amyoclonic seizure, the person is usually awake and able to think clearly.
Like when you are sleepy and you have a sudden movement
How are amino acids neurotransmitters removed from the synaptic cleft?
You have to get rid of the transmitter - this is done (for the amino acid transmitters) by TRANSPORTERS
These take the amino acids back into the terminal and other transporters take it back into the synaptic vesicles
You then use sodium-potassium pumps to bring it back to resting membrane potential
