Neurophysiology 2 Flashcards
Quickly describe the process of converting the electrical AP to a chemical signal in the Presynaptic terminal (~3 steps).
- AP moves into presynaptic region and opens voltage-gated Ca2+ channels
- Ca2+ is released into the presynaptic terminal bulb where it almost immediately signals to the already docked synaptic vesicles to fuse with the membrane
- Fusion b/t synaptic vesicles and membrane occurs allowing release of neurotransmitter into the synaptic cleft.
What role do these proteins play in preparing synaptic vesicles for release?
- Transmitter transport proteins
- Proton Pump
- Transmitter transport proteins: Get transmitters into vessicle
- Proton Pump: Pumps H+ ions into the vesicle when too many neg. charged transmitters are loaded into a single vessicle and the neg. charge becomes limiting. H+ neutralizes charge & allows more transmitters to be loaded into the vesicle.
What role do these proteins play in preparing synaptic vesicles for release?
- Synapsin I
- Calmodulin-dependent kinase II
- Synapsin I: Interacts with actin filaments to guide the vesicle to exactly where it needs to be.
- Calmodulin-dependent kinase II: Plays role in membrane targeting at NT release site.
What role do these proteins play in preparing synaptic vesicles for release?
- Synaptotagmin
- Synaptobrevin
- Synaptotagmin: Binds to Ca2+, enable fusion of vesicle to membrane
- Synaptobrevin: Assists in binding to docking site and membrane for NT endocytosis.
What are SNAP-25 and Syntaxin?
T-snares: proteins on target membrane taht interact with vessicle proteins (V-snares) to dock and eventually fuse with vesicle to allow for neurotransmitter release.
What are Synaptotagmin and synaptobrevin?
V-snares: proteins on vesicle that interact with proteins on the target membrane (T-snares) to dock and fuse w/ to release transmitters.
What happens in docking of vesicle to membrane?
A loose association b/t V and T-snares form. The V-snare synaptotagmin loosely associates with PIP2 in target membrane. Stay in this position until activated further by Ca2+
Describe the fusion process of vesicle and presynaptic membrane.
- Ca2+ binds to synaptotagmin causing a conformational change.
- “Synaptotagmin forces its elbows into the membrane.” This along w/ torque generated during conformational change leads to fusion and release of neurotransmitter into synapse.
What are the two different types of vesicle-membrane fusions that occur? Do they differ in the amount of neurotransmitter released?
- Flattening: Vesicle nearly flattens, completely emptying before being endocytosed from the membrane and recycled.
- Kiss & Run release: Only fuses for short time. Incomplete emptying of neurotransmitter
Botox is a deadly neurotransmitter inhibitor. How does Botox toxin work?
Botox cleaves V-snare and T-snare proteins. Particularly Synaptobrevin (V-snare), SNAP-25 and Syntaxin (T-snares). Vesicles can’t bind plasma membrane to release transmitter into synapse –> Death.
What are 3 mechanisms by which neurotransmitters are cleared from the synapse?
- Enzyme degradation (e.g. acetylcholinesterase)
- Messages can be transported back into presynaptic terminal for recycling
- Diffusion away and out of the synapse
Describe Ionotropic receptors.
Ionotropic receptors
-Ligand-gated ion channels
-Has agonist binding region and pore region
-Very fast - low msec
Basically isotropic receptors are activated by neurotransmitters and open to directly allow inflow of specific ions to propagate a signal. May be stimulating (depolarizing) or inhibitory (hyperpolarizing).
Ionotropic P2X receptor are key mediators of dental pain. How are they stimulated?
P2X receptors are stimulated by ATP!
- ATP is believed to be release from inflamed dental tissue
- ATP initiates action potentials at P2X2 & P2X3
Describe Metabotropic receptors.
Metabotropic receptors:
- Associated with G-proteins, tyrosine kinases etc
- Receptor initiates multiple steps before changing membrane potential
- Much slower than ionotropic receptors but can have longer modulating effects
- Important for signal amplification
- Links to depolarization or hyperpolarization more variable b/c more steps
Describe the mechanism for release of intracellular Ca2+ via the metabotropic-IP3 pathway.
- Stimulated receptor activates Gq-alpha
- activated Gq-alpha subunit activates Phospholipase-C (PLC)
- PLC activates IP3
- IP3 binds to membrane on ER
- Ca2+ released from ER
- Mediates many actions
