5 and 6 - Synaptic Transmission Flashcards
What is an electrical synapse?
A conductive link between two neurons that is formed at a narrow gap between the pre and post synaptic neurons, known as the gap junction
What is the morphology of an electrical synapse?
Each cell contributes a “half channel” called a connexon
What is a connexon formed by?
Six protein subunits called connexoins
What is a gap junction?
A connection between two cells that is formed by the connexon channels
A signal is passed from cell to cell via connexon channels
Is synaptic transmission bidirectional or unidirectional?
Mostly bidirectional, but it can be unidirectional
What is the function of a gap junction?
Rapid transmission of a signal with little or no delay
Groups of neurons that are interconnected by gap junctions have ___________ activity
Synchronous
What is a chemical synapse?
- Specialized junctions through which neurons signal to each other and to non-neuronal cells such as those in muscles or glands.
- Allow for the formation of circuits with the CNS (muscle control, perception, etc.)
What is the morphology of a CNS chemical synapse?
A synaptic cleft forms (10-20 nm space)
- Pre-synaptic density (docking complex)
- Postsynaptic density
- Active zone
What is the active zone?
Part of the presynaptic membrane that is specialized for vesicular release of the transmitter
What is the morphology of a CNS neuromuscular junction?
A synapse between a motor neuron and a muscle fiber
- presynaptic structure
- postsynaptic membrane
Describe the presynaptic structure of a neuromuscular junction
The motor neuron axon approaches its termination, loses its myelin sheath and divides into a number of terminal “boutons”
Describe the postsynaptic membrane of a neuromuscular junction
You will find junctional folds and the motor end plate
What is a synapse?
The site of functional apposition between neurons where an impulse is transmitted from one neuron to another
What is a pre-synaptic neuron?
A neuron before or proximal to the synapse
What is a post-synaptic neuron?
A neuron after a synapse
What does “one-way conduction” mean?
Signals are transmitted from pre-synaptic neurons to post-synaptic neurons ONLY - never vice versa
Describe the mechanism by which an action potential causes transmitter release
- Action potential causes depolarization of the membrane of the pre-synaptic terminal
- This action potential causes Ca++ channels to open
- Ca++ flows into the cell
- This increases the probability that the synaptic vesicles in the active zone will fuse with the pre-synaptic membrane
- Once synaptic vesicles fuse, they release the transmitter
What is the role of SNARE proteins?
- A transmembrane protein that comes together with other SNAREs to form a helical docking complex
- Located on the presynaptic neuron and holds the synaptic vesicle to the membrane until Ca++ release
- Upon Ca++ release the vesicle fuses to the membrane to release the neurotransmitter
What is the SNARE protein of clinical relevance?
It is a vulnerable target for neurotransmitter inhibitors (medications/drugs)
What is the active zone of a chemical synapse?
Part of the presynaptic membrane that specializes in vesicular release of the transmitter
What is the docking complex?
The high concentration of vesicles that “dock” at the tip of the presynaptic neuron
Where does the SNARE complex function?
Near the docking complex because it holds the vesicles close to the membrane so they can be easily released upon Ca++ signaling
What is a synaptic delay?
A pause in the transmission of a signal
What are the three things that can cause a synaptic delay?
1 - Fusion of a synaptic vesicle with the presynaptic membrane
2 - Diffusion of a transmitter across the cleft
3 - Activation of the post-synaptic channels
What type of receptors are associated with short delay times? Ionotropic or metabotropic receptors?
Ionotropic receptors
Is the synaptic delay shorter at chemical synapses or electrical synapses?
Shorter at chemical synapses
think chem = fast
What are the three mechanisms of removing neurotransmitters from the synaptic cleft?
1 - Diffusion away from the cleft
2 - Destruction of the neurotransmitters by enzymes
3 - Transmitter re-uptake either into the synaptic bouton or adjacent astrogilia
What is the first step in the transmission of a neuromuscular signal?
- Pre-synaptic terminal is depolarized
- Ca++ rushes into the cell
- Synaptic vesicles fuse and release Ach
What is the effect of Ach release?
- Ach diffuses across the cleft and binds to Ach receptors at the end plate
What happens once Ach binds to its receptor on the end plate?
- The Ach receptor channel is permeable to Na+ and K+, but more Na+ flows in than K+ flows out
What is the result of uneven ion flow?
Depolarization
Depolarization of the end plate occurs (EPP - end plate potential)
What happens when the depolarization spreads?
- Depolarization spreads to skeletal muscle membranes and causes an action potential to fire
How is the end plate potential (EPP) (AKA depolarization) terminated?
- The EPP is terminated by hydrolysis of Ach by AchE (acetylcholinesterase)
What is the role of AchE?
Cleave Ach - it is an enzyme that gets rid of the neurotransmitter to prevent continual stimulation (need some checks and balances)
Once the Ach is cleaved by Ach, choline still remains in the extracellular space. What happens to it?
It gets taken up into the motor neuron
What is ESPS?
ESPS = excitatory postsynaptic potential
What does ESPS mean?
The neurotransmitter will have an excitatory response when it binds to the receptor because it is an excitatory-type receptor
What is the significance of the ionotropic glutamate receptor?
- The major excitatory neurotransmitter in the brain and spinal cord is glutamate
- Ionotropic means that when the neurotransmitter binds, it directly changes ion permeabilities
- Sooooo…. This is an excitatory receptor that changes ion permeability
What ion permeabilities are affected by the ionotropic glutamate receptor?
- The receptors are permeable to both Na+ and K+, but far more permeable to Na+
- Once glutamate has bound to the receptor, the channel is opened and the larger permeability to Na+ results in a net influx of Na+ down its electrochemical gradient
What is the effect of this net influx of Na+ down its electrochemical gradient?
Depolarization of the membrane - ESPS (excitatory post-synaptic potential), which is a LOCAL potential
What is ISPS?
ISPS = inhibitory post-synaptic potential
What does ISPS mean?
The neurotransmitter will have an inhibitory response when it binds to the receptor because it is an inhibitory-type receptor
What is the significance of GABA?
GABA = the major inhibitory neurotransmitter in the brain and spinal cord
What are GABA receptors permeable to?
Cl- and K+
What happens when GABA binds to an inotropic GABA receptor?
- In most neurons, the potential for Cl- is more negative than the membrane potential
- Binding to the receptor causes an increase in the Cl- permeability
- Cl- flows into the cell
- The membrane becomes hyperpolarized (opposite direction of depolarized and therefore not excitatory, but inhibitory)
What else can happen when GABA binds?
K+ can flow out of the cell, hyperpolarizing it, moving it farther away from threshold and therefore exhibiting an inhibitory function
What is temporal summation?
Occurs when a single presynaptic terminal has two or more action potnetials in rapid succession
The first postsynaptic potential has not died away when the next one occurs - this temporal overlap enables the potentials to sum
What is spatial summation?
Occurs when two or more separate postsynaptic potentials reach the initial segment simultaneously
The initial segment is usually the most electrically exitable part of the neuron (with the lowest threshold for action potential generation)
What are the two types of receptors that acetylcholine can bind to?
1 - Nicotinic receptors
2 - Muscarinic receptors
What are the three neurotransmitters that are considered to be biogenic amines?
1 - Catecholamines
2 - Indoleamine
3 - Imidazoleamine
What are the three types of catecholamine neurotransmitters?
1 - Dopamine
2 - Norepinephrine
3 - Epinephrine
What type of receptor does dopamine bind to?
A dopamine receptor
What type of receptor does norepinephrine bind to?
An adrenergic receptor or a noradrenergic receptor
What type of receptor does epinephrine bind to
An adrenergic receptor or a noradrenergic receptor
There is only one type of indoleamine. What is it?
Serotonin
What type of receptor does serotonin bind to?
5-HT receptors
There is only one type of imidazoleamine. What is it?
Histamine
What type of receptor does histamine bind to?
Histamine receptor (subtypes H1, H2, H3, H4)
There are three types of amino-acid neurotransmitters. What are they?
GABA
Glycine
Excitatory amino acids (glutamate and aspartate)
What does GABA stand for?
Gamma-aminobutyric acid
What type of receptor does GABA bind to?
There are two… GABAa and GABAb
How are the GABAa and GABAb receptors different?
GABAa is a Cl- gated channel
GABAb is a K+/Ca++ channel
What is unique about GABA?
It is present in high concentrations throughout the CNS and is the MAIN CNS inhibitory transmitter
What is important about glycine?
It is the simplest amino acid
What type of receptor does glycine bind to?
An ionotropic receptor that opens Cl- gated channels
What type of an effect does glycine have?
Inhibitory
What are the two excitatory amio acids?
Glutamate and aspartate
What are the receptors for glutamate?
mGluRs (8+ of this type)
AMPA
Kinate
NMDA
What does exocitoxicity mean?
Neurons can be overexcited and destroyed by unusually high amounts of glutamate - causes neuronal damage from oxygen deprivation
Occurs when glutamate and aspartate build up in the extracellular space
What is another name for amino acid neurotransmitters?
Small molecule neurotransmitters
What are the three small molecule transmitters again?
GABA
Glycine
Excitatory (glutamate, aspartate)
What type of transmitters are formed from purines?
Purinergic neurotransmitters and neuromodulators
What is an example of a purinergic neuromodulator?
Adenosine
How does adenosine function as a modulator?
It is part of ATP, which is present in the release of synaptic vesicles
It is able to bind to purinergic or adenosine receptors and act as a depressant in the CNS
What is the receptor for adonosine called?
Purinergic receptors, AKA adenosine receptors
How would you block adenosine receptors?
Since adenosine is a depressant in the CNS, it can be blocked by caffine, theophyline (found in tea) and theobromine (chocolate)
What type of an effect do adenosine receptor blockers have on the CNS?
Stimulatory effect
What are neuroactive peptides?
Peptides that can act as hormones or neurotransmitters or neuromodulators
What are the different types of neuropeptides?
- Opioid peptides
- Substance P
- Vasopressin
- Oxytocin
- VIP-related peptides
What are the three types of opioids that are endogenous (natural)?
Endorphins, enkephalins and dynorphins
What is the only gaseous neurotransmitter?
Nitric oxide - NO
What is unique about the synthesis and release of NO?
Once it is produced, it cannot be contained in synaptic vesicles, so it is released as soon as its made… It will diffuse out of the cell and affect nearby cells
How is NO controlled and stopped?
It decays spontaneously by reacting with oxygen so it is very short lived
What are two examples of endocannabinoid transmitters?
- Anandamide
- 2-arachidonylglycerol (2-AG)
How are endocannabinoids produced?
By the degradation of membrane lipids
How is the transmitter action of endocannabinoids ended?
It is ended by reuptake
What are the two endocannabinoid receptors?
CB1 and CB2
What is the most common type of G-coupled receptor in the brain?
CB1
What does the THC (active portion) of marijuana bind to in the brain?
Both CB1 and CB2 receptors
How do neuropeptides differ from small molecule neurotransmitters in synthesis and release mechanisms?
Neuropeptides
- Synthesized by the nucleus
- Transported down the axon in vesicles
- Reach the nerve terminal for release
Small molecule neurotransmitters
- Synthesized directly in the nerve terminal
- No vesicles or transport before release from the nerve terminal
What is the usual effect (excitatory or inhibatory) of glycine?
Inhibitory
What is the usual effect (excitatory or inhibatory) of GABA
Inhibitory
What is the usual effect (excitatory or inhibatory) of glutamate?
Excitatory
What is the usual effect (excitatory or inhibatory) of aspartate?
Excitatory
Which type of receptor (ionotropic or metabotropic) is faster?
Ionotropic
Which type of receptor (ionotropic or metabotropic) is a ligand-gated ion channel receptor?
Ionotropic
Which type of receptor (ionotropic or metabotropic) is a G-protein coupled receptor?
Metabotropic
What is the effect of a G-protein coupled receptor being activated?
(Metabotropic receptor)
The G-protein can affect the conductance of a channel by opening or closing the ion channel
What is the effect of a ligand-gated ion channel receptor being activated?
(Ionotropic receptor)
Binding of the neurotransmitter directly changes the channel’s permeability to ions (doesn’t have to first activate the G-protein)
This is why Ionotropic is faster - it is a more direct method
Can a postsynaptic neuron have receptors for more than one kind of neurotransmitter?
YES
What does the excitatory or inhibitory effect of a neurotransmitter depend on?
The TYPE of receptors found on the postsynaptic cell
What is myasthenia gravis?
An autoimmune disease that results in muscle weakness and paralysis
What does the autoimmune response attack?
Nicotinic Ach receptors
Is myasthenia gravis a problem with the pre or postsynaptic process?
Postsynaptic - it is a receptor problem
Symptoms of myasthenia gravis tend to worsen with ___________
Activity
In myasthenia gravis, why is the lowered number of nicotinic Ach receptors detremental?
The end-plate potential (EPP) is smaller than normal and so the skeletal muscle cells are not able to generate an action potential
What is Eaton-Lambert syndrome?
An autoimmune disease that results in muscle weakness or paralysis and is commonly seen in cancer patients
What type of cancer patients are at risk for developing Eaton-Lambert syndrome?
Lung and breast cancer patients (small cell carcinoma)
What does the autoimmune response attack?
The voltage gated Ca++ channels
Is Eaton-Lambert Syndrome a problem with the pre or post synaptic process?
Presynaptic - it is a voltage gated channel problem
What is the effect of the botulinum toxin on the body?
Botulinum toxin interferes with the release of neurotransmitters and causes muscle weakness that can cause paralysis of respiratory muscles
What is the molecular mechanism of the botulinum toxin?
It cleaves SNARE proteins on the PREsynaptic terminal which interferes with the release of neurotransmitters
What is alpha-bungarotoxin?
A component of snake venom
What is the molecular mechanism of alpha-bungarotoxin?
It is a neurotoxic protein that is known to bind irreversibly and competitively to the nicotinic acetylcholine receptor found at the neuromuscular junction
What is the effect of alpha-bungarotoxin on the body?
Causes paralysis, respiratory failure and death in the victim
Does the alpha-bungarotoxin affect the pre or post synaptic terminal?
It is a receptor blocker - POST synaptic
Which of the four clinical conditions are considered to be autoimmune disorders?
Myasthenia gravis
Eaton-Lambert Syndrome
Which of the four clinical conditions act on the presynaptic terminal?
Eaton-Lambert (voltage gated Ca++ channel) Botulinum toxin (SNARE proteins)
Which of the four clinical conditions act on the postsynaptic terminal?
Myasthenia gravis (nicotinic Ach receptor) Alpha-bungarotoxin (nicotinic Ach receptor)
