Synaptic communication Flashcards
1
Q
What do we know about ion channels?
A
- the DNA letters (exact sequence of nucleic acids) that encode these proteins in numerous species
- the exact string of amino acids that form these proteins
- their precise 3 dimensional shape
2
Q
How can we test if an amino acid is important for selectivity of an ion channel?
A
- alter the DNA sequence and change the protein
- synthesizing this strand of DNA in the lab and then injecting it into a cell; get cell to make our modified version of this protein
3
Q
How can cells read foreign DNA and make the corresponding protein?
A
- if we attached a gene promoter region to the start of the DNA to tell the cell this gene should be read
4
Q
What are gene promoters?
A
- regions of DNA that initiate gene transcription
- indicate which cells should read the gene and when (instructions)
- different gene promoters are found just before every protein-encoding gene in the genome
5
Q
What are hydrated ions?
A
- When dissolved in water, ions get surrounded by water molecules
- encased by a hydration shell
6
Q
How is it that an ion channel can be permeable to K+ but not Na+? How do potassium ion channels only let in the bigger element?
A
- Ion channel selectivity filters are precisely designed to replace the hydration shell of a particular ion
- K+ ions are equally happy when inside the pore of a potassium ion channel or when surrounded by water
- Na+ ions are too small to comfortably fit (unhydrated) in the pore of a potassium ion channel, so they prefer to stay outside of those ion channels with their hydration shell intact
7
Q
How many voltage gated potassium channels are there?
A
- 40
- no perfect voltage- gated potassium channel
- each cell can choose to express one or any combination of them to optimize cell function
8
Q
What are the 2 types of cells in the central nervous system?
A
- neurons
- glia
9
Q
What are neurons responsible for?
A
- the electrical signals (action potentials) that communicate information about sensations and movements
10
Q
What are glial cells?
A
- serve a variety of support functions for neurons
11
Q
How many neurons and glia are in the human brain?
A
- estimated 85 billion of each
12
Q
What are the 4 types of glial cells in the CNS?
A
- astrocytes
- ependymal cells
- microglia
- oligodendrocytes
13
Q
What are astrocytes?
A
- provide a structural matrix
- physically surround synapses and blood vessels
- regulate the ionic composition of the extracellular solution
- help with neurotransmitter clearance
- regulate blood flow and nutrient distribution in response to changes in neural activity
14
Q
What are ependymal cells?
A
- line the fluid filled ventricles at the center of the brain and spinal cord
- circulate cerebrospinal fluid
15
Q
What are microglia?
A
- the smallest glial cells
- the brain’s clean-up crew; removing dead cells and other debris
- serve an immune function and protect the brain from invading microorganisms
16
Q
What are oligodendrocytes?
A
- produce the myelin sheath
- extend branches of their cell membrane
- each branch wraps many times around a nearby axon
- create many
17
Q
What is myelin sheath?
A
- a wrapping of fat (glial cell membrane)
- electrically insulates the axon
- speeds up conduction of the action potential
18
Q
What are the nodes of Ranvier?
A
- 1 micron gap
- exposed segments of myelinated axons
- only places where myelinated axons feel a charge difference between inside and out
19
Q
How are ions distributed within a cell?
A
- equal except right by cell membrane
- inside, negative charges hug cell membrane
- outside, positive charges hug cell membrane
20
Q
How is the charge distributed within an axon?
A
- charge distributed across axon, weakening over time
- no one ion making the distance, all step over at same time
- right before action potential dies off, it hits the next node which launches the next action potential
21
Q
What is the impact of myelination?
A
- speeds up conduction of the action potential 20x
- The amplitude of the action potential (+40 mV) is regenerated at each node of Ranvier because this is the only place where myelinated axons can access extracellular fluid
- speed of the action potential also depends on the thickness of the axon
22
Q
Where are all the voltage-gated ion channels in a myelinated axon concentrated?
A
- at the nodes of Ranvier
23
Q
What is saltatory conduction?
A
- Action potentials in myelinated axons appear to jump from one node of Ranvier to the next
24
Q
Which axons have the fastest action potentials?
A
- thick, myelinated
- 100 meters/second
25
Which axons have the slowest action potentials?
- thin, unmyelinated
- 1 meter/second
26
What is a synapse?
- junction between the axon terminal of the sending neuron and the cell membrane of the receiving neuron
27
What can happen when a neurotransmitter activates a receptor on the receiving neuron?
- consequence can be excitatory, inhibitory, or modulatory
27
What are synaptic vesicles?
- contain molecules of neurotransmitter
- dock at presynaptic membrane and release neurotransmitter into the synaptic cleft
28
What is the synaptic cleft?
- space between the pre- and postsynaptic membrane
29
What is the presynaptic membrane?
- axon terminal of the sending neuron
- where neurotransmitter is released from
30
What is the postsynaptic membrane?
- membrane of the receiving cell that is opposite the axon terminal
- neurotransmitters released from presynaptic membrane flow across the synapse to postsynaptic membrane, where they bind and activate receptors
31
What is electron microscopy?
- allows us to see small anatomical structures such as synaptic vesicles
32
The diameter of things
0.001 mm - 1 micron (um) = 1000 nanometers (nm)
- small synaptic vesicle: 30 nm
- typical protein: 3 nm
- mitochondria: 1 um
33
small synaptic vesicle
- job to breakdown neurotransmitter
- can hold 5000 molecules
34
What is a ligand?
- a signalling molecule that binds to a receptor
35
What are ligand receptor interactions?
- signalling within and between cells
36
What are the 2 categories of neurotransmitter receptors?
- ionotropic receptors
- metabotropic receptors
37
What is a binding site?
- place on a receptor where a ligand binds
38
What is an ionotropic receptor?
- a ligand gated ion channel and a receptor
- ion channel that opens in response to ligand binding
- Its effects on the membrane potential are very brief and peak within a few milliseconds (instant and fast)
39
What is a metabotropic receptor?
- receptor that is NOT an ion channel
- g protein coupled receptor
- ligand binding typically triggers an intracellular g protein signalling cascade, which can have diverse effects on cell function
- signalling cascades take time, and effects are usually not evident for at least 100ms if not much longer
40
What are intracellular receptors?
- receptors located inside the cell
41
What are surface receptors?
- receptors located on the cell membrane
42
What are the 2 types of surface receptors?
- postsynaptic receptors
- presynaptic receptors
- extrasynaptic receptors
43
What is a postsynaptic receptor?
- receptor located on postsynaptic membrane
- Can be ionotropic or metabotropic (most synapses contain both)
44
What is a presynaptic receptor?
- receptor located on presynaptic membrane
45
What is a extrasynaptic receptor?
- receptor located near but outside a synapse
46
How is neurotransmitter signalling in the synapse kept brief?
- diffusion
- enzymatic deactivation
- reuptake
They stop neurotransmitters from reaching the end of the synapse or clear them away they do
47
What is diffusion?
- Passive movement from areas of high concentration to areas of low concentration
- always happening
- some neurotransmitters leave synapse and float away
48
What is enzymatic deactivation?
- Destruction of a neurotransmitter by an enzyme
- put protein in synapse to break down neurotransmitters
49
What is reuptake?
- Reuptake transporters recycle neurotransmitters by pulling them back into the cell that just released them
50
What is postsynaptic potential?
- when a neurotransmitter binds to a postsynaptic receptor and changes the membrane potential of the postsynaptic cell
- can be fast or slow
- can be excitatory or inhibitory
51
What is a fast postsynaptic potential?
- Ionotropic receptors produce rapid postsynaptic potentials (1 to 5 ms)
52
What is a slow postsynaptic potential?
- Metabotropic receptors do not always produce postsynaptic potentials, but when they do, they are relatively slow/delayed (~100ms to 10s)
53
What is an excitatory postsynaptic potential?
- EPSP
- the result of positive sodium ions entering the postsynaptic cell, causing membrane depolarization and perhaps an action potential
54
What is an inhibitory postsynaptic potential?
- IPSP
- the result of negative chloride ions entering the cell, causing membrane hyperpolarization and fewer action potentials
55
What is depolarization?
- membrane potential of cell becomes less negative than at rest
- the opening of Na+ ion channels will depolarize a neuron, making it more likely to spike
56
What is hyperpolarization?
- When the membrane potential of a cell becomes more negative than it normally is at rest
- The opening of Cl- ion channels can hyperpolarize a neuron, making it less likely to spike
57
Are ionotropic receptors excitatory or inhibitory?
- classified as excitatory or inhibitory based on whether they let in Na+ or Cl- ions and thus cause EPSPs or IPSPs
58
Are metabotropic receptors excitatory or inhibitory?
- classified as excitatory or inhibitory, based on whether they cause the opening of Na+ or Cl- (g protein-gated) ion channels
- some open potassium ion channels (make cell closer to -90mV so inhibitory?)
59
How does a membrane depolarize?
- Sodium ions must enter the cell at a faster rate than potassium ions leave
60
What is neural integration?
- The interaction of the excitatory and inhibitory synapses on a particular neuron
- When EPSPs and IPSPs occur at the same time, the influx of negatively charged chloride ions diminish the impact of the positively charged sodium ions
- cancel each other out, no action potential
61
What determines if a neurotransmitter is excitatory or inhibitory?
- some cells express excitatory nt receptors, while other cells express inhibitory nt receptors
- it is the receptor that is expressed by the postsynaptic cell that determines whether a neurotransmitter will be excitatory or inhibitory, not the neurotransmitter itself
- we often describe neurons as being excitatory or inhibitory because we know they reliably cause EPSPs or IPSPs in the downstream cells they connect to
62
How does the neural circuit work?
- sensory neuron spikes, sends electrical message down to axon terminal in spinal cord
- release of neurotransmitter from sensory neuron will depolarize and cause action potential in excitatory interneuron, activates motor neuron and cause reflex
BUT
- neuron in cerebral cortex can send action potential to spinal cord to excite an inhibitory interneuron
- release of nt from inhibitory interneuron will hyperpolarize motor neuron and counteract reflex
- contest between two competing drives
63
What's the difference between neural and behavioural excitation?
- inhibitory neuron is a neuron that reliably causes IPSCs in downstream neurons
- firing of an inhibitory neuron does not always inhibit behaviour
- Inhibition of inhibitory neurons can generate motor behaviour
- For every neuron trying to change behaviour in one way, there are other neurons trying to do the opposite
- hard to determine which ones are trying to cause or prevent a behaviour
- The firing of excitatory neurons deep in the brain does not necessarily cause movement, and the firing of inhibitory neurons does not necessarily inhibit movement
64
What is a receptor protein?
- A protein that is sensitive to a stimulus and passes along the message
- It can be a neurotransmitter receptor or a receptor for something else
- either ionotropic or metabotropic
65
What is an ionotropic receptor?
- receptor that is an ion channel
- Its activation has an immediate consequence on the cell’s membrane potential; causes an EPSP or an IPSP depending on whether the pore of the ion channel is permeable to Na+ or Cl-
66
What is a metabotropic receptor?
- receptor that is not an ion channel
- typically triggers an intracellular signaling cascade involving g proteins
- activation can have large or small effects on any cellular process, but the effects won’t be instantaneous, since they depend on intracellular signaling and diffusion
- All g protein-coupled receptors (GPCRs) are metabotropic receptors
67
What cellular processes can metabotropic receptors affect?
- opening ion channels
- changing gene expression
- secretion of substances
- cell growth
- cell division (not in neurons)
- cell death
- anything the cell wants
68
What is a g protein?
- use GTP molecules, instead of ATP, for the energy they need to catalyze a chemical reaction
- molecular switches
- when bound to GTP they are ON
- while on they can catalyze reactions, lasts between 10 secs and several minutes
- on is temporary because g proteins convert GTP to GDP, becoming off
- hard time letting go of GDP
- need an activated metabotropic receptor to let go of GDP
69
What is the activation cycle of g proteins?
- the cycle starts when a ligand finds a metabotropic receptor
- ligand binding to metabotropic receptor induces a conformational change that helps the g protein let go of GDP allowing it to bind a molecule of GTP
- the g proteins diffuse away to trigger chemical reactions
- At some point the g protein will convert GTP to GDP
- It will then go back to the metabotropic receptor and wait
70
What are g protein gated ion channels?
- ion channels that are gated by g proteins
71
How is a g protein gated ion channel opened?
- a signaling molecule has to activate a metabotropic receptor
- allowing a g-protein to become activated
- activated g protein can bind (directly or indirectly) to a g-protein-gated ion channel
- ion channel will open, letting ions in
* metabotropic receptors can cause the opening of many g protein gated ion channels at once
72
Where can synapses form?
- between an axon terminal and smooth dendrite (a dendritic shaft)
- between an axon terminal and a dendritic spine
- between an axon terminal and a soma
- between an axon terminal and another axon terminal (axoaxonic synapse)
73
What are axoaxonic synapses?
- synapse between axon terminal and another axon terminal
- regulate the amount of neurotransmitter that the second neuron will release when it has an action potential
74
What is presynaptic inhibition?
- axoaxonic synapses can hyperpolarize the axon terminal of the downstream neuron, so its voltage-gated calcium channels will not open as much as they normally do when the there is an action potential
- The net effect is to reduce neurotransmitter release from the downstream when it has an action potential
75
What is presynaptic facilitation?
- Axoaxonic synapses can depolarize the axon terminal of the downstream neuron, so that its voltage-gated calcium channels are more likely to open when an action potential arrives
- The net effect is to increase neurotransmitter release from the downstream neuron when it has an action potential
76
What is an autoreceptor?
- a receptor located on presynaptic membrane that makes the cell sensitive to its own neurotransmitter release
- gated by the release of neurotransmitter from the cell they are in
- always metabotropic and inhibitory
- main source of presynaptic inhibition
77
What is a postsynaptic receptor?
- receptor located on the receiving neuron
