Synapses; NT Release; Metabotropic Receptors; Synaptic Modulation: Module 2.3-2.5 Flashcards
What are the 2 types of synapses?
- Electrical
- Chemical
What is characteristic of an electrical synapse image?
Membranes touching leaves no space for vesicles.
What are the distinctions between electrical and chemical synpases?
Distance Between Membranes
- Electrical Synapses: 3nm
- Chemical Synapses: 30nm(neuronal) - 50nm(nerve-muscle)
What channels generate the current in the post synaptic cell in synaptic transmission at an electrical synapse?
Voltage Gated Ion channels in the Presynaptic Cell.
Is Electrical Transmission Graded?
Yes. It occurs even when the current in the presynaptic cell is below the threshold for an action potential.
Where was the first electrical synapse found?
Crayfish Giant Motor Synapse
What are the functions Gap junctions?
- Connect Two Cells wiht a large and unselective pore (Allows everything to pass)
- They allow the passage of ions small molecules as large as 1kDa
- They provide pathways for both chemical and electrical communication
In Chemical - They allow NT precursors to be transferred between neurons
Explain the Gap Junction Structure.
- Two apposed hexameric structures called connexons, one contributed by each cell.
- Connexons contact eachother to bridge a gap of 3nm between membranes.
- Connexon has six identical subunit surrounding a central pore - radial hexameric symmetry.
- Each subunit is called a connexin(Cx) - Molecular of 26-46 kDa.
- Diameter of Pore has diameter of 1.2 - 2nm
- Cytoplasmic end of connexon - funnel shaped entrance.
What are reciprocal synapses?
Gap Junctions that pass electrical current in both directions with equal frequency.
What is the current type(IV plot relation) passing through the gap junction?
Ohmic
How do gap junctions arrange at the membrane?
Forms Plates with very little membranes left.
Explain the mechanism of Gap Junction(Connexon) gating.
Increases in [Ca2+]i can cause gap junctions to close.
In the absence of Ca2+, the pore is in an open configuration and the
connexin subunits are tilted 7 - 8 degrees from an axis perpendicular to
the plane of the membrane. After the addition of Ca2+, the pore closes
and the subunits move to a more parallel alignment. The gating of the
gap junction channel may thus correspond to a conformational change
that involves concerted tilting of the six connexin subunits to widen
(open) or to constrict (close) the pore.
Are Connexin Subunits diverse?
Yes
Every Tissue(Smooth Muscle. Epithelia) can have gap junctions.
Different types of Connexins in Each one
What are the 4 different type of gap junctions?
Homo/Hetero meric - For a given connexon hexamer - Same or Different Connexins
Homo/Hetero Typic - Apposition of idential or different connexon hexamer.
What are connexin hemichannels?
Connexin hemichannels are half of a gap junction channel. Each hemichannel, or connexon, is a hexameric assembly of six protein subunits called connexins. These hemichannels are embedded in the plasma membrane of a cell and serve as a conduit between the intracellular and extracellular environments.
Involved in Pathological Conditions
Describe the synapse of the neuromuscular junction.
The axon of the motor neuron
innervating the muscle ramifies into
several branches. Each branch forms
synaptic boutons (swellings). The
boutons lie over a specialized region of
the muscle membrane, the end-plate,
and are separated from the muscle
membrane by a 100-nm synaptic cleft.
Synaptic vesicles clustered around
active zones, where the
neurotransmitter acetylcholine (ACh) is
released. Immediately under each
bouton in the end-plate are several
junctional folds, the crests of which
contain a high density of ACh
receptors.
What are synaptic boutons and dendritic spines?
- Synaptic boutons are small swellings that are found at the terminal ends of axons. Synaptic boutons are the sites where synapses are
found and is where neurotransmitters are stored in vesicles. - Dendritic spines are protrusion from a neuron’s dendrite thatreceives a synaptic input from an axon. It is the side of the synapse where neurotransmitter receptors are located.
Dendritic Spines are Highly Dynamic
Variable ____ and volume correlates with the ____ of each spine synapse.
Variable spine shape and volume correlates with the strength and maturity (size of EPSP) of each synapse.
What shape of dentritic spine has stronger response?
Shapes with more volume.
What are the different types of dentritic shapes?
Note one denrite can have many spines with many different shapes
How many vesicles and NT are in typical presynaptic chemical synapses?
Typically contain 100 to 200 synaptic vesicles each of which contain several thousand NT.
What does amplification in chemical synapses refer to?
Chemical transmission lacks the speed of electrical synapses, but it amplifies signals: one synaptic vesicle releases several thousand of transmitter that together can open thousands of ion channels in the target cell.
Describe the process of synaptic transmission at chemcial synapses.
What are the two types of post synaptic receptors?
What are the two biochemical features that all receptors for chemical transmission have?
- They are membrane-spanning proteins that recognize and binds the transmitter.
- They carry out an effector function within the target cell
Who discovered quantal release of neurotransmitter?
Fatt, Euler, Axelrod,
Novel Prize in 1970
What are miniature end-plate potentials?
Electrophysiological “noise” - Tiny Depolariztions = 0.4mV
Size of these suggested that they occur in discrete multiples of unitary amplitude
What is an inhibitor for AchE?
Neostigmine.
Is Ach release quantized?
Yes, MEPPs led to this finding, quantum event corresponds to ACh release from one synaptic vesicle.
Miniature end-plate potentials
What factor does amplitudes of end plate potentials increase by?
0.4 mV
Corresponds with 1 more vesicle being released each time.
What is the equation that describes the mean number of quanta releasd after a single impulse?
Where does the main delay of chemical transmission come from?
Delay of Ca Influx
Need accumulatin of Ca in the Presynaptic to cuause release of vesicles.
What is Amperometry?
Presynaptic detection of neurotransmitter release by carbon fiber electrode.
Explain Capacitance measurements as an indicator exo/endocytosis and NT release.
Release of vesicles increase membrane area which increases capacitance that we can measure to quantify release of NT.
What is the sniffer patch technique?
Outside Out Membrane Patch expressing a high density of the dsired receptors. Voltage Clamped
Another electrode stimulated neuron of interest, releaseing NT on the detector patch.
What technique of measuring is used to determine what NT is released?
Sniffer Patch Technique
What type of curve/relationship does presynaptic Ca have on transmitter release?
Sigmoid shape on a logarithmic scale.
Eventually has a max. (Limited # of Vesicles)
Explain the structure of how vesicles are attached to the membrane.
What Protein does Ca bind to for vesicle release?
Synaptotagmin
Explain how Ca binds to Synaptotagmin.
Is an integral vesicle membrane protein that act as Ca Sensors. Needs to bind 5 Ca to activate. C2A Subunit Binds 3, C2B Binds 2.
The short N-terminal tail (the vesicle lumen), is followed by a single hydrophobic domainm(vesicle membrane) and a long cytoplasmic tail that contains two C2 domains (C2A and C2B) near the C terminus. The C2 domains are calcium- and phospholipid-binding motifs.
Explain the zippering process of the synaptotagmin-complexin-SNARE complex.
Describe the SNARE complex structure?
Consists of a bundle of four a-helixes, one each from synaptobrevin and syntaxin and two from SNAP-25.
What are the steps of the formation and dissociation of the SNARE Complex?
- Synaptobrevin interacts with two plasma membrane target proteins, the
transmembrane protein syntaxin and the peripheral membrane protein SNAP-25. - The three proteins form a tight complex bringing the vesicle and presynaptic
membranes in close apposition (see part B). Munc18 binds to the SNARE
complex. - Calcium influx triggers rapid fusion of the vesicle and plasma membranes; the
SNARE complex now resides in the plasma membrane. - Two proteins, NSF and SNAP (unrelated to SNAP-25), bind to the SNARE
complex and cause it to dissociate in an ATP-dependent reaction
What is the active zone?
The active zone is a specialized region of the presynaptic neuron at the synapse where neurotransmitter release occurs. It is a highly organized structure located within the presynaptic membrane, facing the synaptic cleft and directly opposite the postsynaptic density. This zone is crucial for efficient synaptic transmission.
What are the three filamentous structures of the active zone and how are they organized?
- Pegs
- Beams
- Ribs
Where are the Cav channels in relation to the active zone machinery?
Structure over area of membrane with Cav channels lined up with the pegs and ribs.
What does a G-coupled receptor (GPCR) have the ability to do?
Have the ability to bind and hydrolyze guanosine triphosphate (GTP) to GDP.
Do transmitters one have one type of receptor they act on?
No, many transmitters have both types of receptors that they act on.
Explain the G protein activation cycle.
What is the function of AC (Adenylyl Cyclase) and what activates and inhibits it?
Converts ATP to cAMP, which when then activate protein Kinase A.
Activated by Alpha stimulatory subunits from g-proteins.
Inhibited by Alpha inhibitory subunits from g-proteins.
What is phototransduction and what is the G-protein mechanism?
Phototransduction is the biological process in which light is converted into electrical signals in cells.
Mechanism:
How does G-proteins act via phospholipase?
What are the two levels of amplification in chemical synapses?
- Presynaptic: Neurotransmitter release
- Metabotropic Receptors: Signalling Pathways
Metabotropic Amplification Example
Can one neurotransmitter have a variety of divergent effects?
Yes, can activate multiple receptors stimulating different pathways. Can affect different neurons or different parts of a neuron differently depending on receptor types expressed.
What does it mean when it says neurotransmitters can have convergent effects?
Multiple transmitters, each activating its own receptor type, converge on a singe type of ion channel in a single cell and stimulate the same effect.
What is an example of a convergent effect in pyramidal cells of the hippocampus?
GABA, 5-HT1A, A1 (adenosine),
and SS (somatostatin) receptors, all of
which activate the same K+ channel.
NE, ACh, 5-HT, corticotropin-releasing
hormone, and histamine all converge
on and depress the slow Ca2+-
activated K+ channels.
Given that brain modulatory systems differ in structure and funtion:
What are the 4 similarities of all brain modulatory systems?
- Small set of Neurons (several thousand) forms the center of the system.
- The neurons of the system arise from the central core of the brain; mostly from the brainstem.
- Each neuron influences many others; has an axon that contacts more than 100,000 postsynaptic neurons across the brain.
- The synapses are designed to release transmitters widespread into ECF to act on mny neurons instead of a single synaptic cleft.
IPSP and EPSP are all done through ionotropic receptors.
Where do all synaptic modulatory systems originate from and what are some examples of these systems?
The brainstem.
What synpatic modulatory pathway is indicated by the image below and how does it work?
The Norepinphrine System (Locus Coeruleus)
Axons arising from the locus
coeruleus synapse on pyramidal
cells in the cerebral cortex,
where they release NE.
NE acts on β-adrenergic
receptors in the pyramidal cell
membrane. NE inhibits multiple
K currents. The effect of NE by
itself has little or no influence
on the activity of a resting
neuron. However, a cell exposed
to NE will react more powerfully
when it is stimulated by a strong
excitatory input (usually
glutamatergic).
Thus, NE modulates the cell’s
response to other inputs.
What is the NE system involved in?
- Regulation of Attention
- Arousal
- Sleep-Wake Cycle
- Learning
- Memory
- Anxiety
- Pain
- Mood
- Brain Metabolism
What effect does NE have on pyramidal cells?
Increases Neuronal excitability in pyramidal neurons via B-Andregenic Receptors and PKA.
Tunes up response of Cells
What are the 2 cellular sites at which modulation by second messengers can occur?
Presynaptic: Second Messengers can regulate efficacy and duration of transmitter release in turn effecting the size of the PSP.
Example: Altering Ca influx by directly modulating Cav channels or indirectly modulatng K channels which alters Ca influx.
Postsynaptic: Second Messengers can elter directly the amplitdue of the PSP by modualting ionotropic receptors.
