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67 Cards in this Set

  • Front
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Define Synapse
Specialized functional junction for communication between a neuron and another neuron or effector organ.
3 Types of synapses based on the communicating ends:
1. Neuro-neuronal
2. Neuromuscular
3. Neuroepithelial
2 Ways that signal transmission can occur at synapses:
1. Through bridged junctions
2. Through unbridged junctions
How does signal transmission occur at Bridged junctions?
Via Gap junctions (cell-cell channels)
How does signal transmission occur at Unbridged Junctions?
Over Synaptic clefts that are APPOSED but discretely SEPARATE.
What is the typical direction of flow at a synapse?
Unidirectional - from pre to postsynaptic element.
What is required for bidirectional flow of a signal?
Electric coupling via gap junction.
What are the 3 main modes of synaptic transmission?
1. Electrical
2. Chemical
3. Gaseous
How is Electrical transmission mediated?
By direct flow of current via gap junctions.
How wide is the gap junction between cells electrically coupled?
3.5 nm
What does each cell contribute to the gap junction structure?
A hemi(half)-channel called a CONNEXON
What is the pore diameter size in a gap junction?
1.5 nm
What is a connexon made up of?
6 subunit CONNEXINS
What is the structure of a connexin like?
4 membrane-spanning regions
So what is the structure of a gap junction?
2 Connexons -> 12 connexins -> 48 membrane-spanning regions!
Why are Gap Junctions good for electrical conductance?
-Low resistance
-High conductance
-Bridge the two cells' cytoplasms.
What happens when current flows from the presynaptic neuron thru the gap junction?
It depolarizes the postsynaptic cell.
What is special about these electrical synapses?
They are the most rapid form of synaptic communication b/c there is virtually no synaptic delay!
What is the nature of the AP generated at the synapse?
All-or-none - the stereotypical AP.
What type of functions are Chemical synapses involved in?
-Developmental
-Regulatory
How can electrical transmission be regulated?
It can't be regulated or inactivated.
What is a major difference between Electrical and Chemical synapses?
Chemical synapses have a HIGH DEGREE of MORPHOLOGICAL SPECIALIZATIONS at the pre/post synaptic cell membranes.
List 3 morpholog specializations in presynaptic chemical synapses:
1. Synaptic vesicles
2. Active zones
3. Autoreceptors/receptors
What are Active Zones?
Sites on the presynaptic membrane where there are dense projections.
What are 2 types of postsynaptic specializations?
1. Receptors
2. Postsynaptic density - PSD-95
What are the 4 types of Chemical synapses in the CNS?
1. Gray's type I
2. Gray's type II
3. Monoaminergic
4. Peptidergic
For a Gray's Type I Synapse:
-Vesicle shape
-Cleft size
-Signfct postsynaptic feature
-Another name
Vesicles = round
Cleft = Wide
PSD = prominent
Assymetric synapse
For a Gray's type II Synapse:
-Vesicle shape
-Cleft size
-Signfct postsynaptic feature
-Another name
Vesicles = flat/pleomorphic
Cleft = narrow
PSD = less prominent than I
Symmetric synapse
For a Monoaminergic Synapse:
-Vesicle features
-Cleft size
-Signfct postsynaptic feature
Vesicles = dense-core
Axons have varicosities
Cleft = Wide
-No pre/postsynaptic densities
Main feature of peptidergic synapses:
Large Dense-core vesicles
What are the 6 important features of the NMJ?
1. Presynaptic dense bars
2. Calcium channels
3. Primary/2ndry Synaptic clefts
4. Postsynaptic junctional folds
5. AcH receptors facing the Active Zone
6. AcHesterase/Basal Lamina in clefts
How many steps are involved in Chemical Transmission?
9
What are the nine steps of chemical transmission?
1. Synthesis
2. Prepare vesicles for docking
3. Interaction of membranes
4. Fusion
5. Release of NT
6. Diffusion of NT
7. Binding of NT to receptors
8. Postsynaptic cell response
9. Termination of NT
What has to be synthesized in order for chemical transmission to occur?
Where does it usually happen?
1. NT
2. Channel proteins
3. Synaptic vesicles
-usually in the cell body
How are vesicles normally stored in the axon terminal?
Anchored to the cytoskeleton by Synapsin I dephosphorylated.
What releases NT vesicles for docking at the active zone?
Phosphorylation of Synapsin I - releases them from the cytoskeleton.
How do vesicles find their way to the active zone?
With the help of Rab3A
What allows NT vesicles to interact with the presynaptic membrane?
NSF, SNAP, and SNARES
What is the hypothesis for how Snares work?
V-snare binds the vesicle; T-snare binds the target; v-snare binds to t-snare so the vesicle can fuse to PM.
What is NSF?
an ATPase
What is SNAP?
A helper of NSF which utilizes ATP to unravel the snare assembly for vesicle recycling.
What is essential for the vesicle membrane to fuse to the plasma membrane?
CALCIUM
How does calcium mediate synaptic vesicle fusion with PM?
Ca2+ binds Synaptotagmin on the vesicle membrane which triggers rapid fusion.
What happens when Ca binds Synaptotagmin for vesicle fusion with presynaptic PM?
Release of NT by exocytosis!
What is the effect of NT binding receptors on the postsynaptic membrane?
Gating of ion channels are affected.
What is the response of the postsynaptic cell to NT binding receptors on it?
1. Excitatory Postsyn Potential
2. Inhibitory Postsyn Potential
(EPSP or ISPS)
3. Action potential
What are 4 mechanisms of terminating NT action?
1. Diffusion
2. Enzyme hydrolysis (destroy)
3. Bind inhibitory presynaptic autoreceptors (neg feedback)
4. Reuptake to presyn terminal
What is the DETERMINING factor for how a postsynaptic cell will respond to a NT?
The properties of the receptor it binds - excitatory or inhibitory.
By what 2 mechanisms can a postsynaptic NT receptor work?
1. Direct activation of ion channel gating by binding it.
2. Indirect activation of an ion channel by initiating a 2nd msgr cascade.
What is each receptor type?
-Direct gating
-Indirect gating
Direct = ionotropic

Indirect = metabotropic
What is the timing for ionotropic?
Fast time domain
What is the timing for metabotropic?
Slow time domain - involves several steps
What is the effect of a NT binding an ionotropic receptor mediated by?
Mediated by a receptor that is part of the ion cannel itself
How is the metabotropic receptor's effect mediated?
By the receptor being coupled to transduction G-proteins which activate a 2nd msgr cascade.
What are 5 important features of chemical transmission?
1. Amplification
2. Plasticity
3. Diversity - coding
4. Neuromodulation
5. Synaptic delay
What are the 3 types of cell interactions that use Chemical transmission?
1. Neuro-neuronal
2. Neuro-muscular
3. Neuro-effector
What are the 2 types of cell interactions that use Gaseous transmission?
1. Neuroneuronal
2. Neuroeffector
How is Gaseous Synatptic Transmission mediated?
By synthesis and diffusion of a gaseous messenger from the pre to postsynaptic nerve termini.
By what mechanism does gaseous transmission work?
Second Messenger system - cGMP and cGMP-dependent protein kinase.
2 Types of gaseous transmission synapses:
1. Neuroneuronal
2. Neuroeffector
What is the effector generally in neuroeffector gas synapses?
Smooth muscle
What are the steps in Neuroneuronal gaseous synapse?
1. Glu released from presynptic
2. Glu binds NMDA rec on post
3. Ca2+ influx into post
4. Ca binds Calmodulin
5. CAD activates NOS
6. NO has effect on post cell, or neighbor cells.
What is the reaction catalyzed by NOS?
Arginine converted to citrulline + NO
How does Neuroeffector gas transmission differ from neuroneuronal?
NO is produced in the presynaptic cell, not the post.
What are the steps in Neuroeffecter gaseous synapse?
1. AP travels down presyn axon
2. Calcium influx into pre
3. Ca binds Calmodulin, CAD activates NOS
4. NO produced diffuses into smooth muscle
5. NO binds heme moiety on Guanylate Cyclase to effect
What is required for gaseous transmission to work?
-Calcium
-NOS
-Heme moiety - Guanylate Cyclase
-2nd msgr or protein kinase
How does activated Guanylate Cyclase exert its affect?
By activating cGMP dependent protein kinases to indirectly alter ion channel gating.