Module B-04 Flashcards
2 types of synapses
1) electrical
2) chemical
How to electrical synapses conduct?
ions move through membrane spanning gap junctions to the next cell
Describe structure of gap junction channel
- Formed by two hemichannels called Connexons
- Each connexon has 6 subunits called Connexins
- Each connexin has 4 membrane spanning regions
Cells of CNS where electrical synapses occur
1) Hormone-secreting cells of the hypothalamo-pituitary axis
2) Some spinal motor neurons
3) Hippocampal pyramidal cells
4) Mesencephalic nuclear cells
5) Retinal cells
6) connect Astrocytes (K+ buffering and Ca2+ signalling)
Cells of PNS where electrical synapses occur
Schwann cells
Speed and direction of electrical synapses
Fast (0.1 ms) and can be uni or bidirectional
Where does transmitter vesicle release occur in chemical synapses
from presynaptic cells at the ACTIVE ZONE of the synaptic Bouton
3 locations on the neuron where neuronal chemical synapses occur
1) Axodendritic (on dendrites)
2) Axosomatic (on cell bodies)
3) Axoaxonic ( on axon hillock and near synaptic terminal)
________ and __________ synapses are mainly inhibitory
Axoaxonic and Axosomatic
__________ synapses are mainly excitatory
Axodendritic
How do Axosomatic and Axoaxonic inhibition differ?
Axosomatic inhibit Action potential
Axoaxonic inhibit transmitter release (AP do occur)
What are Tripartite synapses
occur btw astrocyte , postsynaptic and presynaptic neuron
What is role of Astrocyte in Tripartite synapses?
uptake of transmitter released and release others fr uotake by neurons (eg glutamate to glutamine)
5 traditional criteria for substance to be classified as neurotransmitter:
- synthesis in presynaptic neurons
- storage in preparation for release
- release by presynaptic neurons, typically in a calcium-dependent fashion
- binding to specific postsynaptic receptors
- removal from synapses by specific mechanisms
5 groups of LOW molecular weight neurotransmitters:
1) Acetylcholine
2) Monoamines
3) Amino Acids
4) Purines
5) Gases
3 Groups of Monoamines and examples
1) Catecholamines- Dopamine, Norepi and Epi
2) Indoleamines - Serotonin and Tryptamine
3) Others - Histamine and taurine
5 amino acid neurotransmitter
1) Glycine
2) Glutamate
3) Aspartate
4) Homocysteine
5) GABA
4 Purine neurotransmitters
1) Adenosine
2) ATP
3) ADP
4) AMP
2 Gases neurotransmitters
1) NO
2) CO
Describe synthesis of Low Molecular weight Neurotransmitters
- synthesized in cytosol
- loaded into clear vesicles (some in dense core vesicles)
- tethered to cytoskeleton near active zone
Describe synthesis of High Molecular weight Neurotransmitters
- synthesized in soma as propeptides
- transported by anterograde axonal transport in Large dense core vesicles
- converted along the way into multiple transmitter molecules
- the vesicles are stored further away from active zones
- eg : opioid peptides of pain regualtion
Describe synthesis of Nitric Oxide (NO) Neurotransmitter
- Ca2+ enters cell through NDMA receptor
- Ca2+-Calmodulin complex forms => activates NO synthase => converts L-arginine to L-citrulline and NO
Isoform of NO synthase in neurons
nNOS
Is NO stored?
no , it is synthesized on demand by Ca release which can come from presynaptic neuron
How is Dopamine loaded into vesicles
by a H+- Dopamine antiport on vesicular membrane
What tethers vesicles to cytoskeleton?
Synapsin
How are vesicles released from cytoskeleton
Phosphorylation of synapsin by calcium calmodulin-dependent protein kinase
How are vesicles moved towards active zone for exocytosis?
by Rab proteins
How do vesicles dock on nerve terminal membranes?
a. Vesicular membranes have v-SNARE proteins and the nerve membrane has t-SNARE proteins
b. v-SNARE protein synaptobrevin binds to t-SNARE protein
syntaxin
c. v-SNARE protein synaptotagmin binds to t-snare protein neurexin
How is neurotransmitter released after vesicle docks?
vesicular membrane protein Synaptophysin forms the fusion pore in the nerve terminal membrane
What is the role of Ca2+ in neurotransmitter release?
- release of vesicle ( indirect phosphorylation of Synapsin)
- opening of inserted fusion protein
How is return of Ca2+ to normal levels (the slower falling phase)?
- Ca2+ ATPase and a Ca2+/Na+ exchange system
- Sequestration of Ca2+ ions within the smooth endoplasmic reticulum and mitochondria of the nerve terminal
When are low and High mol weight transmitters co released
- low nerve stimulation rates (100 Hz), the rise in [Ca2+]i
spreads further, thereby promoting exocytosis of the large dense core vesicles
Describe recycling of small clear vesicles
- Endocytosis mediated by the protein clathrin,which coats the vesicle.
- Once internalized, the vesicles lose their coats and fuse
with the endosome, which forms new vesicles for refilling
Describe recycling of dense core vesicles
- endocytosis.
- The empty vesicles are transported retrogradely to the soma for refilling
2 categories of receptors
1) Ionotropic
2) Metabotropic
What happens to an ionotropic receptor upon binding of a neurotransmitter?
- causes conformational change
- either opens or closes central ion passing pore
- changes ionic conductance which affects membrane potential
examples of ionotropic receptors
Nicotinic AChR;
GABAA receptor;
NMDA receptor for glutamate
What happens to an metabotropic receptor upon binding of a neurotransmitter?
- binding of neurotransmitter causes dissociation of G protein subunits => interact with second messenger
- signaling cascades activate kinases, liberate calcium and promote phosphorylation of channels for K+, Ca2+ or Cl-
examples of metabotropic receptors
muscarinic AChR
norepinephrine receptors
____________ receptors have short lived and faster action
Ionotropic
____________ receptors affect metabolism and gene expression
Metabotropic
