Synaptic transmission Flashcards
What are the two types of synapses?
Electrical
Chemical
What are the two types of chemical synapses?
Neuron-neuron
Neuron-muscle
Electrical synapses are made up of what membrane proteins? Where are these from (which cells)?
Connexons–one from each neuron participating in the synapse
How many connexins make a connexon?
6
Are most electrical synapses uni or bidirectional?
Bidirectional
How fast are electrical synapses?
Extremely fast
Why do electrical synapses have a low selectivity?
Connexons allow water and ions to pass through without any specific selection (size is only selection)
How do electrical synapses relate to chemical synapses?
They mediate chemical synapses
What are the four ways that neurons can transmit chemical signals?
- Endocrine
- Paracrine
- Synaptic
- Autocrine
What is autocrine signalling for neurons?
Receptors on pre-synaptic cell for transmitter it releases
What is a neuromodulator?
chemical messenger that can affect release of neurotransmitter or the receptor function of a neurotransmitter. Some chemicals can be both neurotransmitters and neuromodulators.
What is paracrine signalling?
Signals released to local cells
What organelle is always found in presynaptic synapses?
Mitochondria b/c there is a high energy need
Are neurotransmitters in presynaptic neurons made on the spot or are they stored?
Stored in vesicles
The influx of what ion leads to release of the neurotransmitters in vesicles?
Ca
What are the transmembrane proteins that hold chemcial synapses togehter?
Neurexins
Are chemical synapses unidirectional, or bidirectional?
Unidirectional
True or false: in influx of Ca ions in the presynaptic bouton causes a moderate-major change in [Ca]
False-very small and localized
The increase in [Ca] in the presynaptic bouton causes what to happen?
Release of neurotransmitters
True or false: the neurotransmitter that is released from the presynaptic bouton always causes channels in the postsynaptic cleft to open
False–can open or close
What are the steps in the recovery phase of a chemical synapse? (3)
- Repolarization of presyapse via K= efflux
- Ca channels close
- Ca removed from cleft
What are the roles of SNARE proteins in synaptic transmission? (2)
Form a complex between the vesicle and the presynaptic cell membrane
Sensors of Ca
How is Ca removed from its localized position in the presynaptic neuron? (4)
- Diffusion
- Ca binding proteins
- Transported into internal Ca stores
- Pumped out
How are the vesicles recycled in presynaptic membranes?
Through clatharin mediated endocytosis
Why is it possible to deplete chemical neurons?
It takes 1 minute to replenish vesicles
What are the three major small-molecule neurotransmitters?
Amino acids
Acetylcholine
Amines
What are the two different type of amines that are neurotransmitters?
Monoamines
Catecholamines
What are the two responses to neurotransmitter binding on the postsynaptic bouton? What are the two processes that can take place?
excitation or inhibition
Depolarization or chemical cascade
What are ionotropic receptors?
Ligand gated ion channels on the postsynaptic membrane
What are metabotropic receptors?
G-protein coupled receptors
Are metabotropic receptors faster or slower acting than ionotropic receptors?
Slower
True or false: A postsynaptic neuron can have receptors for more than one kind of neurotransmitter
True
The major excitatory neurotransmitter in the brain and spinal cord is of what type?
Glutamate
What is the pore that glutamate opens? Which way do ions flow?
Na/K pore, which lets some K out, but a lot of Na in
What happens to the postsynaptic neuron when glutamate binds to its channel (depolarization or hyperpolarization)?
Depolarization (d/t net influx of Na) and thus excitation
What does it mean that the depolarization caused by a single glutamate receptor is decremental?
It is only local, and will not elicit a depolarization event by itself
What is the primary inhibitory neurotransmitter in the nervous system?
GABA
True or false: Metabotropic receptors can cause excitatory effects in several ways
True
Ionotropic GABA receptors are permeable to what ion? What happens when these open?
Cl-
This causes CL to flow down its [C] gradient into the neuron, and hyperpolarize it
If ECl- is more negative than resting membrane potential, which is the case for most neurons, then increasing Cl- permeability causes Cl- to flow where?
Into the cell
What would happen to a postsynaptic neuron if a metabotropic receptor caused K channels to open (and a subsequent efflux of K)?
Hyperpolarization
How can metabotropic receptors effect a depolarization through K or Cl channels?
Decrease the permeability of the channels
What is a synaptic delay?
Time interval between when action potential invades the pre-synaptic terminal and when a membrane potential change begins in the post-synaptic cell
Which type of synapse has a longer delay: chemical or electrical?
Chemical
What are the three ways in which transmitters are removed from the synaptic cleft?
Diffusion
Enzymatic degradation
Reuptake/transport
What is the MOA of cocaine?
Binds to the dopamine reuptake protein ono the presynaptic neuron, and prevents reuptake
What is the target of SSRIs?
5HT transporters
What is the target of MAOIs?
Monoamine oxidase (the enzyme that oxidizes 5HT
What is the target of TCA (tricyclic antidepressants)
5HT transporter
What is temporal summation?
When the same presynaptic neuron gives a signal in rapid succession to elicit a response in the postsynaptic neuron
What is spatial summation?
When two or more separate neurons create signals that are given together to elicit a postsynaptic response
What is synaptic efficacy?
how big an effect a synapse has on the postsynaptic cell.
What is synaptic plasticity?
“the ability of synapses to strengthen or weaken over time, in response to increases or decreases in their activity” - wiki
What is a neuromuscular junction?
A specialized synapse between a motoneuron and a muscle fiber
Where does the mylein sheath end in a neuronmuscular juncation?
Just before the synaptic bouton
What is the major difference in neuromuscluar junction presynapses, as compared to CNS synapses?
There are multiple active zones within the presynaptic terminal
What organelle is found in high amounts in the presynaptic terminal of a neuromuscular junction?
Mito
What is the major difference in neuromuscluar junction postynapses, as compared to CNS synapses? What is the purpose of this?
There are many junctional folds
What is the only neurotransmitter found in neuromuscular junctions? Receptor?
Acetylcholine and its nicotinic receptor
What is the MOA of nicotinic acetylcholine receptors?
Allows for the influx of Na (and smaller efflux of K), activating Na channels elsewhere
How is acetylcholine degraded?
Acetylcholine esterases
What is the end plate depolarization?
The depolarization that takes place in neuromuscular junctions
What is the function of anticholinesterases?
Inhibit acetylcholine esterase, and prolong the EPP
Why are neuromuscluar junctions considered “safe and reliable”?
since in a normal, healthy person an action potential in the motor neuron always causes an action potential in the skeletal muscle fibers it synapses on
Why is reuptake of choline essential for motor neurons?
This is necessary since motor neurons cannot synthesize choline and choline does not pass through cell membranes easily.
What type of receptor is the nicotinic acetylcholine receptor? What are the ions that this uses, and how?
Ligand gated channel (ionotropic).
Increases permeability of K and Na, but more so to Na
What type of channel is used in the reuptake of acetylcholine?
Secondary active synporter (with Na as the opposing ion)
How many motor neurons innervate a skeletal muscle?
One, and only one
Are there inhibitory synapses at neuromuscular junctions?
No–ONLY excitatory
When you talk about inhibiting a skeletal muscle cell this means what?
that the alpha motor neuron innervating that cell is inhibited.
Why do neuromuscular junctions need to ensure that the signal they send is strong (which they do via multiple terminals, multiple active zones, etc.)?
Becauses there is a 1-1 ratio of motor neurons to muscle fibers
What is the MOA of botulina toxins? What are the symptoms of botulina poisoning?
Proteinase that cleaves the SNARE complex associated with vesicles in the presynaptic neuron. Thus vesicles will not be held near the end of the synapse
Symptom = flaccid paralysis
What is the MOA of tetanus?
Cleaves the SNARE protein of glycine neurotransmitters (interneurons) of neurons in the spinal cord
What is Eaton-Lambert syndrome?
An autoimmune attack on voltage – gated Ca++ channels in the terminals of somatic motor nerves. This inhibits vesicle release
What is the MOA of myasthenia gravis?
autoimmune disease which reduces the number of acetylcholine receptors at the postsynaptic neuromuscular junction
What is the autoimmune disease discussed in lecture that affects presynaptic channels?
Eaton-Lambert syndrome
What is the autoimmune disease discussed in class that affects postsynaptic channels?
Myasthenia gravis
What is the MOA of neostigmine in treating myasthenia gravis?
Reversibly inhibits acetylcholine esterase
Where does the muscle weakness of Myasthenia gravis usually appear?
In the face
What are the signs/symptoms of myasthenia gravis?
Muscle weakness, especially if it gets worse in the day.
Neck weakness against physician’s force
What is the MOA of nicotine?
Agonist of the nicotinic acetylcholine receptors
What is the MOA of bungaroo toxin? Symptoms?
Irreversible binding/blocking of nicotinic acetylcholine receptors. Causes paralysis
What is edrophonium used for? MOA?
Used to diagnose myasthenia gravis.
Short acting, reversible cholinesterase inhibitors
What is the MOA of sarin?
Irreversibly binds acetylcholine inhibitors
True or false: irreversible inhibition of acetylcholine receptors is always poisonous
True
What are the three features a neurotransmitter must have to be defined as a neurotransmitter?
- Packed into a vesicle
- Ca-dependent release
- Binds to specific receptors
What are the three major categories of neurotransmitters?
- Small molecule
- Neuroactive
- Gaseous neurotransmitters
What is the unconventional neurotransmitter that does not fit into the three major classes of neurotransmitters?
Endocannabinoids
Which class of neurotransmitter is Acetylcholine?
Small molecule
What is the receptor for acetylcholine at neuromuscular junctions?
Nicotinic acetylcholine receptor
What are the two major types of acetylcholine receptors?
Nicotinic (fast, ionotropic)
Muscarinic (slow, metabotropic)
Which type of neurotransmitters are biogenic amines classified as?
Small molecule
What are the three biogenic amines?
- Catecholamines
- Serotonin
- Histamine
What are the three catecholamines discussed in lecture?
Dopamine
Norepi
Epi
(all share common Y derivation)
What type of receptors for epi and norepi bind to?
Adrenergic/noradrenergic receptors
What defines a catecholamine? Is 5HT a catecholamine?
All share a common Y derivative
5HT is NOT a catecholamine, but is a biogenic amine
What type of neurotransmitter is serotonin? What amino acid is it derived from?
biogenic amine
Derived from W
What type of neurotranmitter is histamine?
biogenic amine
What are the amino acid neurotransmitters?
- GABA
- Glycine (G)
- Glutamate (E)
- Aspartate (D)
What is the major inhibitory neurotransmitter?
GABA
What are the two main classes of GABA?
A and B
What is the receptor for GABAa?
ligand gated Cl- channel
What is the receptor for GABAb?
a metabotropic receptor which has an inhibitory effect by opening K+ channels or suppression of Ca++ channels.
What is the efffect of glycine (inhibition or excitation)?
Inhibition
What type of receptor does Glycine bind to?
Ion gated Cl- channel
What is the effect of strychnine?
Blocks Glycine receptors
What are the two excitatory amino acid transmitters?
E and D
What are the three different classes of glutamate receptors?
AMPA
Kainate
NMDA
What ion blocks the NMDA in Glutamate pathways until the postsynaptic membrane is slightly depolarized through stimulation of other excitatory receptors.
Mg
The NMDA receptor channel (that binds glutamate) is permeable to what three ions?
Ca, Na, and K
What receptor is believed to have an important role in memory and learning
Glutamate
What is excitotoxicity?
Destruction of neurons by an unusually high accumulation of glutamate and related compounds
What are the four types of “small molecule” neurotransmitters?
Acetylcholine
Amino acids
Purines
Biogenic amines
What are the purine neurotranismitters?
ATP and Adenosine
Is adenosine stored in vesicles?
No
What is the general effect of adenosine?
Depressant
What is the MOA of caffeine, theophylline, and theobromine?
All block adenosine
What are the receptors for adenosine called?
Adenosine receptors
What does ATP (as a neurotransmitter) bind to
P-type purinergic receptors
Where are peptide precursor molecules that act as neurotransmitters synthesized? Where do they complete their maturation?
Synthesized in the nucleus, then packed into vesicles with enzymes and sent down neuron where they mature
Where are small molecule neurotransmitters usually synthesized?
At the end of the axon
Neuropeptides can coexist in same nerve terminals with classic transmitters. What causes their release?
LARGE amounts of Ca (They are not released at active zones since the vesicles are too large to fit into the docking complex)
What type of neurotransmitter are opioids?
Neuropeptide
What type of neurotransmitter are vassopressin and oxytocin?
Neuropeptides
What are the three endogenous opioid families?
Endorphins
Enkephalins
Dynorphins
What is the one gaseous neurotransmitter?
NO
How is NO produced?
by the action of the enzyme nitric oxide synthase
How NO synthase regulated?
The enzyme is regulated by Ca++ binding to the Ca++ sensor protein calmodulin.
True or false: NO is contain in synaptic vesicles
False- it is released as soon as it is made to affect nearby cells
What class of neurotransmitter are ananamide and 2-arachidonylglycerol?
Endocannaboids
How are endocannaboids produced?
Via enzymatic degradation of membrane lipids
What are the two types of endocannaboid receptors?
CB1 and CB2
What does THC bind to?
CB1 and CB2
