What is a characteristic of the electrical synapses that distinguish them from chemical synapses?
Electrical synapses connect a large group of neurons together, so signals can e passed in a very fast manner
Where are peptide neurotransmitters made and where are they released?
In the cell, released from Golgi
Where are non-peptide neurotransmitters made?
In the nerve terminal
Where are vesicles released from?
Golgi
What is the role of calcium in vesicle release?
Voltage gated calcium channels in the presynaptic membrane opens when AP reaches in the terminal, this allows calcium to flow down the electrochemical gradient and Ca2+ controls the fusion of vesicle and mobilization of the vesicles
What is the role of synapsins in vesicle release?
Synapsins in resting state, bind vesicles to actin filament
When do synapsins release vesicles from binding to actin?
When Ca2+ enter the neuron
What is the role of Rab protein in vesicle release?
Binds GTP and guides the freedup vesicle to move to the active zone
What is the SNARE complex?
Formed by protein on the vesicle – snaptobrevin (VAMP) and membrane proteins (SNAP 25 and Syntaxin)
What is the role of SNARE Complex?
Docks the vesicle to the presynaptic membrane
What is the role of Munc18?
Protein in the presynaptic membrane that is required for exocytosis of the synaptic vesicles
What happens if Munc18 is not present?
Vesicle would not be able to fuse to membrane
What is the role of synaptotagmin?
It is a protein on the vesicle that sense calcium and binds to calcium which triggers the fusion of vesicle, pore formation and NT release
What is the role of NSF?
To recycle vesicles and disassemble the SNARE complex
How do clostridial toxins disrupt vesicle release?
They target and cleave VAMP, therefore inhibit the release of Ach at NMJ resulting in paralysis
What are some examples of clostridial neurotoxins?
Tetanus and botulinum toxins
How do alpha-latrotoxins disrupt vesicle release?
This is a spider toxin that binds to neurexin which results in massive calcium influx inside the neuron and consequently lead to a massive release of vesicle depletion and Ach release.
What are some symptoms as a result of the alph-latrotoxin (spider toxin)
Acetylcholine related sxs such as pain, muscle rigidity, vomiting and sweating
What are some methods to terminate neurotransmission?
Diffusion
Enzymatic degradation
Reuptake
What is the transporter that is used for glutamate reuptake?
Na+/K+ exchange, no chloride dependence
Na+ and glutamate into cell, K+ out
What is the transporter for other neurotransmitters reuptake?
Na+ and Cl- cotransport
Na+, Cl- and NT all into cell
What are the vesicular uptake transporters used for monoamines?
VMAT 1 and VMAT 2
What is the vesicular uptake transporter used for GABA?
VGAT
What is the vesicular uptake transporter used for Acetylcholine?
VAchT
Which ion gradient do plasma membrane transporters utilize for reuptake of neurotransmitters?
Na+ gradient
Which ion gradient do vesicular transporters use for reuptake of neurotransmitters?
H+ gradient
What does Acetylcholine breaks down into?
Acetate and choline
What enzyme is involved in the breakdown of acetylcholine?
Acetylcholinesterase
Serotonin reuptake utilize which ion gradient?
Na+ gradient
What is the enzyme responsible for degrading serotonin inside the presynaptic terminal?
MAP
What does serotonin break down into?
5-HIAA (5-hydroxyindoleacetic acid)
What is the role of astrocyte in synaptic transmission?
It wraps around the synapse and has NT receptors, and when bound to NT, Ca2+ increases intracellularly and release transmitters of their own that can either enhance or inhibit synaptic activity
What is the cause of Lambert-Eaton Myasthenic Syndrome (LEMS)?
An autoimmune disorder in which antibodies against voltage0gated Ca2+ channels in the presynaptic terminals is affected. Preventing motor neurons from sending Ach to muscles
What part of body is affected by LEMS?
Skeletal muscles weakness
What receptors are found on postsynaptic membrane in neuromuscular junction?
Nicotinic ionotropic receptors
What is an ionotropic receptor and how does it differ from metabotropic receptor?
Ionotropic is ligand-gated, once a ligand binds, the channel is activated. Metabotropic requires a second messenger and thus it is slower in nature
What ion enters the postsynaptic neuron once the nicotinic receptor is activated by Ach binding?
Na+ ion enters and leads to depolarization of the muscle end plate
Which neurotransmitters have receptors in the same ligand-gated receptor family and what is the characteristic of said receptor?
GABA, Acetylcholine and glycine
5 subunits each with 4 transmembrane alpha helices
What is the characteristic of the glutamate receptor?
Ligand-gated receptor that has just 4 subunits each with 3 trans membrane alpha helices
What is the characteristic of gap junctions?
Formed by hemichannels with 6 subunits each with 4 transmembrane regions
What is the characteristic of voltage gated channels?
4 subunits each with 6 transmembrane domains
What are some of the groups of metabotropic receptors?
G-protein coupled
Receptor tyrosine kinases (RTKs)
What is the characteristic of Transient Receptor potential (TRP) channels?
Similar to voltage-gated in that each subunit has 6 transmembrane domains but these are not voltage-gated. Sensitive to nociceptive stimuli, some are G protein coupled
How many transmembrane domains are in G protein coupled receptors?
7
What are the ligands for receptor tyrosine kinases?
Peptide hormones (EFG, GFG, NGF, BDNF) and insulin
What type of receptor (metabotropic or ionotropic) is nicotinic receptor?
Ionotropic
What type of receptor (metabotropic or ionotropic) is muscarinic receptor?
Metabotropic
What happens to muscarinic receptor when Acetylcholine binds?
Slow EPSP, leading to decrease outward of K+ current by closing K+ leak channel thus encouraging depolarization
Closes M-type K+ Channel
What happens to nicotinic receptor when acetylcholine binds?
Results in FAST EPSP; leading to decrease outward of K+ current by closing K+ leak channel thus encouraging depolarization
What happens when GIRK is activated by acetylcholine binding to muscarinic receptors on cardiomyocytes?
K+ leaves the cell leading to hyperpolarization thereby slows down heart rate
Is 5-HT1 G-protein coupled channel inhibitory or excitatory?
Inhibitory; effects K+
Is 5-HT2 G-protein coupled channel inhibitory or excitatory?
Excitatory; effects K+
What kind of channel is 5-HT3 and what is its effect?
Ligand-gated channel permeable to Na+, K+ and Ca2+; excitatory
True/False: Neostigmine is used to treat myasthenia gravis because it is an acetylcholinesterase inhibitor.
True
What is the difference between myasthenia gravis and Lambert-Eaton myasthenic syndrome?
In MG, there are antibodies that are against nicotinic acetylcholine receptors binding on the POSTsynaptic membrane, preventing depolarization
In LEMS: antibodies are against Ca2+ voltage gated receptors in the PREsynaptic membrane
