Exam #1: Synaptic Transmission Flashcards
Describe the morphology of an electrical synapse.
An electrical synapse is two neurons connected by one or more gap junctions, which is permeable to ions and small molecules.
- Each opposite cell contributes half a channel, called a semi-channel or connexon
What is a gap junction composed of?
- Each gap junction contains a connexon
- A connexon is formed by six protein subunits, called connexins
How are signals passed between cells at a gap junction?
Electrical & chemical coupling
- Bidirectional
- Fast
- Low selectivity
What are connexins?
Protein subunits of the connexon that makes a gap junction
What are the two types of chemical synapses?
1) Hormone
2) Neurotransmitter
Describe the morphology of a CNS synapse.
- Synaptic cleft is 20-40nm apart
- Pre & post-synaptic membranes are held together by ECM & transmembrane proteins
- Unidirectional transmission
- Can have excitatory or inhibitory effects post-synaptically
Describe the morphology of a neuromuscular junction.
Much larger than the nerve terminal
What is the mechanism by which action potentials cause transmitter release?
1) Transmitter is synthesized & stored in vesicles
2) Action potential invades presynaptic terminal
3) Depolarization causes opening of voltage-gated Ca++ channels
4) Influx of Ca++
5) Ca++ causes vesicles to fuse with presynaptic membrane
6) Transmitter is released into synaptic cleft via exocytosis
7) Transmitter binds to receptor on post-synaptic membrane
8) Opening or closing of post-synaptic channels
9) EPSP or IPSP
10) Removal of NT by glial uptake or enzymatic degradation
11) Retrieval of vesicular membrane from plasma membrane
What is the general role of SNARE proteins?
Several specific transmembrane proteins located at vesicles & on the presynaptic plasma membrane that form a helix complex for vesicle docking & fusion
- Some are Ca++ binding proteins that “sense” Ca++ binding
What is the active zone of a chemical synapse? How do active zones differ in the CNS & NMJ?
The part of the pre-synaptic membrane that is specialized for the vesicular release of neurotransmitter
- Multiple in NMJ
- Single in CNS
Where is the docking complex located & what is its function?
Presynaptic density where vesicles containing neurotransmitters dock
What is synaptic delay?
The pause between the arrival of an action potential in the pre-synaptic terminal and the onset of potential change in the post-synaptic cell
What are the causes of synaptic delay?
- Events leading to fusion of synaptic vesicle with presynaptic membrane
- Diffusion of transmitter across synaptic cleft
- Activation of postsynaptic channels
What type of receptor is associated with short synaptic delay times?
Electrical synapses have a shorter delay than chemical ones
Is the synaptic delay shorter at chemical or electrical synapses?
Electrical
What are the three mechanisms of removing neurotransmitters from the synaptic cleft?
1) Diffusion
2) Enzymatic Degradation
3) Transport back to the pre-synaptic terminal or into neighboring astrocytes (glial cells)
Describe neuromuscular transmission.
1) Motor neuron action potential
2) Ca++ enters voltage-gated channels
3) ACh release
4) Binds NAChR
5) Na+ entry
6) Depolarization of the muscle fiber
7) Depolarization of voltage-gated Na+ channels
8) AP generated & propagated
9) ACh breakdown
What is the role of AChE in neuromuscular transmission?
Breakdown of ACh into acetate & choline
What is an EPSP?
Excitatory post-synaptic potential
Which ion permeabilities are affected during an EPSP?
Both Na+ & K+, but there is a higher permeability to Na+
How does an EPSP cause depolarization?
- Glutamate gated ion channels are permeable to Na+ & K+
- There is a larger driving force for Na+
- EPSP brings Vm closer to firing threshold
What is an IPSP?
Inhibitory post-synaptic potential
Which ion permeabilities are affected during an IPSP?
Cl-
How does an IPSP cause hyperpolarization?
- GABA binds & opens Cl- channel
- Cl- movement inward hyperpolarizes the membrane
What is temporal summation?
When a single pre-synaptic terminal has 2+ action potentials in succession; first post-synaptic potential has not completely diminished when the second comes in & they add
What is spatial summation? How does it differ from temporal summation?
When 2+ separate postsynaptic potentials reach the initial segment simultaneously & their effects add
How do neuropeptides differ from small molecule neurotransmitters?
asdf
Which neurotransmitter is a gas?
NO
Which type of neurotransmitter is created by enzymatic degradation of membrane lipids?
Endocannabinoids
- Anandamide
- 2-arachidonylglycerol
What is the typical effect of glycine?
Inhibitory
What is the typical effect of GABA?
Inhibitory
What is the typical effect of Glutamate?
Excitatory
What is the difference between an ionotropic receptor & a metabotropic receptor?
Ionotropic receptor= ligand gated ion channel i.e. neurotransmitter binds & channel opens
- Rapid changes in membrane potential
- Point-to-point
Metabotropic= g-protein coupled receptors
- Relatively slow change in membrane potential
- Diffuse
- Signaling amplification
How does Myasthenia Gravis affect synaptic transmission? Is the problem pre-synaptic or post-synaptic? Is this an autoimmune disease?
- Autoimmune
- Post-synaptic
- Antibodies against NAChR, an important mediator of EPPs
How does Eaton-Lambert Syndrome affect synaptic transmission? Is the problem pre-synaptic or post-synaptic? Is this an autoimmune disease?
- Often occurs in patients with small-cell carcinoma of the lung (& breast cancer)
- Patients have antibodies to voltage gated Ca++ channels
- Autoimmune & pre-synaptic
- Less Ca++ enters pre-synaptic terminals; thus, less ACh is released, which results in muscle weakness
How does Botulinum toxin affect synaptic transmission? Is the problem pre-synaptic or post-synaptic? Is this an autoimmune disease?
- Botulinum toxins cleave SNARE proteins*
- Vesicles will not properly dock to pre-synaptic membrane
- ACh will not be released
- Symptoms:
1) NMJ paralysis
2) Muscle weakness
*As does tetanus toxin, but tetanus causes tetanic contraction.
How does alpha-bungarotoxin affect synaptic transmission? Is the problem pre-synaptic or post-synaptic? Is this an autoimmune disease?
- A peptide from the venom of a banded krait (snake)
- Irreversibly blocks NAChR
- Post-synaptic
After Ca++ influx into the pre-synaptic nerve following depolarization, how is this Ca++ removed?
1) diffusion
2) Ca++ binding proteins
3) Transported to internal Ca++ stores
4) Pumped outside of the cell
How are vesicles recycled?
Clathrin-mediated endocytosis
How do metabotropic receptors cause excitatory effects?
Decrease conduction through K+ or Cl- channels
How do metabotropic receptors cause inhibitory effects?
Increase conduction through K+ or Cl-
What is the mechanism of cocaine addiction?
- Antagonism of DA transporters
- Increase in DA in the synaptic cleft
What classes of anti-depressants block 5-HT reuptake?
1) Tricyclics
2) SSRIs
What type of receptor is the NAChR?
- Ionotropic
- Permeable to Na+ & K+ (higher permeability to Na+)
What are the unique features of neuromuscular transmission?
1) Only one motor neuron innervates a skeletal muscle fiber
2) Only excitatory input
3) Only one NT, ACh
4) Only on receptor, NAChR
5) Multiple active zones in one terminal
6) Multiple terminals on one muscle fiber
7) Strong synaptic transmission to ensure AP generation
How does Tetanus toxin result in tetanic contraction, while Botulism toxin results in muscle weakness?
- Different target: interneurons (GABA) vs. motor neurons
- Disinhibition of GABA results in hyperexcitation
- Result is tetanic contraction
What are the clinical manifestations of Myasthenia Gravis?
- Ptosis & weakness of smile are early signs
- Development of diplopia & speech slurs through the course of the day
- Inability to resist extension of neck
List the NAChR blockers.
- Turbocuarine
- Cuare
- alpha-bungarotoxin
List a common NAChR agonist.
Nicotine
What are common reversible inhibitors of AChE?
- Edrophonium
- Neostigmine
What are common irreversible inhibitors of AChE?
- Organophosphate poisons
- Sarin nerve gas
