Neurotransmitters 1 Flashcards
Fast, reliable, and bidirectional mode of communication throughout the CNS
Electrical synapses/gap junctions
Electrical synapses/gap junctions allow what type of molecules to pass from one cell into another? What type of passage?
Ions and small molecules (
What proteins form the electrical synapse/gap junction? Be specific in the makeup.
- Connexins, ~20 of them
- 6 connexins form 1 connexon
- 2 connexons align to form a channel
What are electrical synapses important in? List 4.
- Embryonic stem cells
- Retina
- Auditory system
- Cortex
What regulates an electrical synapse? List 4.
- Cytosolic pH
- Cytosolic calcium
- Phosphorylation
- Voltage
This is caused by mutations in one connexin
The most common form of inherited deafness in Caucasian populations (DFNB1)
What do electrical synapses allow?
Allow groups of similar neurons to be synchronized e.g. hormone-secreting neurons in hypothalamus - get burst of hormone secretion; neocortical interneurons; cells of adrenal medulla
Explain the membrane potentials in pre and post-synaptic neurons
- Potential in downstream neuron won’t go as high
- Signal will be degraded
- Signal is less intense, more spread out
- Not faithfully transmitter. Quick, but can’t keep doing this forever
Do electrical synapses have a synaptic delay?
Yes, ~0,1 msec
What is the predominant mode of signaling?
Chemical synapses
Which type of synapse (electrical or chemical) is faster?
Electrical synapses. (Chemical are not quite as fast)
2 key features of a chemical synapse
- Synaptic vesicles
2. Receptors on post-synaptic ending
What is the major different in contact of pre and post synaptic membranes in chemical and electrical synapses?
Electrical synapse-connected by desmosomes, no synaptic cleft, touching each other
Chemical synapse-no direct contact with each other, 2-4x bigger membrane space, contain synaptic cleft ~20 nm
In vesicular release for major neurotransmitters, an action potential propagates down an axon and does what to the presynaptic terminal?
Depolarizes it
What is the consequence of depolarization of the presynaptic terminal in vesicular release?
Opens voltage gated Ca2+ channels
What is the difference in intracellular and extracellular concentration of Ca2+ ?
[Ca2+] outside = mM (10^-3)
[Ca2+] inside = uM (10^-6)
much smaller inside
What initiates fusion of synaptic vesicles with plasm membrane in vesicular release?
Influx of Ca2+. After depolarization, calcium voltage gated channels open and calcium ions enter down their electrochemical gradient. (Equilibrium potential for Ca = ~100 mV)
After fusion of synaptic vesicles with plasma membrane, vesicle content is released into this very small region
Synaptic cleft
What type of receptors on post-synaptic cells do released transmitters act on?
Ligand gated ion channels or receptors that use G proteins (GPCRs)
True or false: Transmitters can only act on receptors on the post-synaptic cell
FALSE. They can also act on receptors on the pre-synaptic terminal
What inactivates transmitter? List 4.
Na+ dependent reuptake, degradation and/or diffusion, or glial metabolism
Vesicular membrane must be retrieved. What two events facilitate this?
Exocytosis followed by endocytosis
Pre-synaptic vesicles contain more than one kind of vesicle. Release from these types has a different Ca2+ dependence and occurs at a different place
Large dense core vesicles (LDCVs)
Calcium is a crucial player of vesicle release. What are two of its sources?
- Usually comes across the synaptic plasma membrane to start release
- Can also be liberated from intracellular space
3 benefits of chemical synapses
- Amplification of signal
- Integration of inputs
- Makes use of different receptors
How do different receptors create a variety of post-synaptic effects?
Ligand gated ion channel-response is RAPID
Other receptors link to signaling pathways that alter morphology, receptor localization, gene transcription- response is SLOWER
Major mode of release
Vesicular release
Most prevalent vesicle, lined up at synapse
Small clear synaptic vesicles (SSVs)
These vesicles are less numerous and not as localized
Large dense core vesicles (LDCVs)
What type of chemical mediators are released by diffusion (non vesicular release)
Lipid mediators like anandamide/endocannabinoids, neurosteroids, and gasses like NO
What type of chemical mediators are released by transport?
Hydrophilic molecules (via carriers or pores)
There are over a hundred different neurotransmitters known. They are split into what two groups?
Smal molecules and peptides
List 5 biogenic amines that fall under small molecules group of neurotransmitters
- Dopamine
- Epinephrine
- Norepinephrine
- Serotonin
- Histamine
List 4 amino acids that fall udner small molecules group of neurotransmitters
- Glycine
- Glutamate
- Aspartate
- GABA
What store small molecule transmitters?
Small clear synaptic vesicles (SSVs)
What store peptides?
Large dense core vesicles (LDCVs)
Which neurotransmitter is present in both types of vesicles?
ATP
Which type of neurotransmitter group is most abundant?
Peptides, far outnumber small molecule transmitters
List and describe the three main features major neurotransmitters share
- Localization (substance must be present at presynaptic site, usually made by that neuron)
- Release (must be released in response to presynaptic depolarization, release dependent on extracellular Ca2+)
- Receptor (on postsynaptic cell, mimicry, given exogenously, get same affect with same amount of substance)
List the 3 approaches for inactivation and which transmitters employ them
- Enzymatic degradation- ACh, peptides
- Reuptake- Dopa, norepi, epi, serotonin, GABA, glycine, glutamate
- Diffusion- Important for all
List the three important catecholamines
Dopamine, epinephrine, norepinephrine
Why use vesicles? (3)
- Concentration of transmitter- makes it high enough to affect receptor following release into synaptic cleft
- Separates transmitter pool from metabolic pool and from degradative enzymes- Glu, Gly, GABA, ACh, catchecholamines
- Essential part of biosynthetic pathway for some transmitters (peptides, norepi and epi)
What is the importance of having vesicles recycle multiple times?
If synaptic vesicles simply fused with presynaptic membrane, the terminal would enlarge and supply of vesicles would be depleted.
Where are synaptic vesicles proteins synthesized?
ER and Golgi, cannot be replenished quickly
The recycling process of synaptic vesicles is fast. ~1 min. List the steps (5)
- Budding from endosome - exocytosis
- Docking - exocytosis
- Priming
- Fusion of calcium (1msec)
- Budding with endoome- endocytosis (10-20 sec)
Vesicles nearby, but not at the terminal
Reserve pool
Some reserve pool vesicles are even further away form terminal, often tethered to actin cytoskeleton by this molecule
Synapsin (on surface)
This type of vesicle is siting right next to plasma membrane at active zone.
Docked vesicles
This type of vesicle is not ready to be released quickly
Docked vesicles