Synapse Structure Flashcards
What is a synapse?
A specialized functional contact zone
(junction) for communication between nerve cells (neuro-neuronal), or between a nerve cell and its effector organ (neuromuscular, neuroepithelial, etc.)
Synaptic transmisssion
- Bridged junction or gap junction
* Unbridged junction: presence of synaptic cleft
Bridged/Gap Junction:
- Bidrectional
* Can be unidirectional
Unbridged junction:
• Unidirectional
presynaptic»_space; postsynaptic
Electrical Transmission
- Gap: only 3.5 nm wide
- Apposing cells each contributes a hemi-channel = connexon
- 2 connexons form an ion channel: pore size of 1.5 nm in diam.
- Each connexon: 6 connexins
- Each connexin: 4 membrane-spanning regions
- Connexins undergo conformational changes to open or close the pore
Electrical transmission is mediated by ______________.
gap junctions
Gap junctions:
- Low-resistance, high-conductance channels bridging the 2 cells
- Current flows through the junction and depolarizes the postsynaptic cell
- Most rapid form of synapse between neurons: virtually no synaptic delay
Properties of electrical synapse:
- Speed of transmission: no synaptic delay
- Synchronization of transmission: 2 or more electrically-coupled neurons
- Contributes to stereotypic, all-or-none behavior
- Transmission of developmental and regulatory signals between cells
- No mechanisms for inhibitory actions
- No mechanisms for long-lasting changes in effectiveness (modulation) of synapses
____________ is the neurotransmitter of the vagus n. to the heart
Ach
___________ is the neurotransmitter of the neuromuscular junction
Ach
Chemical Transmission is mediated by:
release and diffusion of neurotransmitters into the synaptic cleft
Presynaptic (prejunctional):
• Synaptic vesicles
• Active zones:
(presynaptic dense projections)
• Autoreceptors/receptors
Synaptic cleft:
• Typically wider than the extracellular
space; 30-50 nm or more
Postsynaptic (end-plate;
postjunctional):
- Receptors
* Postsynaptic density (PSD-95)
Morphological Types of CNS Chemical Synapses:
Gray’s type I (Asymmetric)
Gray’s type II (Symmetric)
Gray’s Type I (asymmetric):
- Round synaptic vesicles
- Wide synaptic cleft
- Prominent PSDs
- Often associated with excitatory synapses
Gray’s Type II (symmetric):
- Flat or pleomorphic vesicles
- Narrow cleft
- Less prominent PSDs
- Often associated with inhibitory synapses
Monoaminergic synapses:
- Dense-core vesicles
- Axonal varicosities
- Wide synaptic cleft
- No prominent pre- & post-synaptic densities
Peptidergic synapses:
- contain large dense-core vesicles
* Vesicles are of different sizes & shapes
Neuromuscular Junction:
- Presynaptic dense bars
- Ca++ channels
- Primary & secondary synaptic clefts
- AChE and basal lamina in clefts
- Postsynaptic junctional folds
- Ach receptors face active zones
- Voltage-gated Na+ channels along sides and depths of folds
Myasthenia Gravis:
Disease of chemical transmission at the neuro-muscular synapse
• Severe weakness of muscles
Autoimmune: most common Antibodies against one’s own nicotinic acetylcholine receptors (AChR) in muscles. Congenital and heritable: rare
• Treatment: Inhibitors of acetylcholinesterase
What are symptoms of myasthenia gravis?
• Severe weakness of muscles
Autoimmune: most common; antibodies against one’s own nicotinic acetylcholine receptors (AChR) in muscles
Congenital and heritable: rare
How is myasthenia gravis treated?
Inhibitors of acetylcholinesterase
Tetanus toxin:
cleaves VMAP
Botulinum toxins:
cleave VAMP or t-SNARE
α-Latrotoxin:
binds to neurexin
Synapsin I:
- binds vesicles to cytoskeleton
- phosphorylated by Ca2+/calmodulin-dependent protein kinase
- when intracellular Ca2+ is increased»_space; releases vesicles from the cytoskeleton
Rab3A:
- a neuron-specific GTPase
* binds to vesicles essential for propelling vesicles to the active zone
Synaptotagmin:
- has 5 Ca2+-binding sites
* major Ca2+-sensing protein that triggers vesicular exocytosis
NSF:
N-ethylmaleimide-sensitive factor (an ATPase):
• cytosolic
• hydrolyzes ATP to release the complex
v-SNARE (vesicular SNAP Receptor proteins) = VAMP (vesicle-associated membrane protein):
Synaptobrevin: binds t-SNARE
t-SNARE (target membrane SNAP Receptor):
Syntaxin: a plasma membrane protein
SNAP-25: a plasma membrane protein of 25 kDa
What is the process for v-SNARE & t-SNARE associate proteins?
v-SNARE & t-SNARE associate»_space; docking & fusion»_space; NSF & SNAP bind to complex & dissociate it
Neurexin:
plasma membrane protein
may also interact with vesicle proteins
SNAP:
- soluble NSF attachment protein
- unrelated to SNAP-25
- cytosolic
- binds to NSF
Postsynaptic Receptors:
determine postsynaptic response
Common biochemical features:
Common biochemical features:
Membrane-spanning proteins with external recognition sites for specific transmitter molecules.
Effector function triggered in target cell:
• Directly activates gating of ion channel -or-
• Indirectly activates gating through second messenger cascade
• A given transmitter binds to conserved families of receptors and is associated with specific physiological functions
