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
Q
Which axons have the slowest action potentials?
A
- thin, unmyelinated
- 1 meter/second
26
Q
What is a synapse?
A
- junction between the axon terminal of the sending neuron and the cell membrane of the receiving neuron
27
Q
What can happen when a neurotransmitter activates a receptor on the receiving neuron?
A
- consequence can be excitatory, inhibitory, or modulatory
27
Q
What are synaptic vesicles?
A
- contain molecules of neurotransmitter
- dock at presynaptic membrane and release neurotransmitter into the synaptic cleft
28
Q
What is the synaptic cleft?
A
- space between the pre- and postsynaptic membrane
29
Q
What is the presynaptic membrane?
A
- axon terminal of the sending neuron
- where neurotransmitter is released from
30
Q
What is the postsynaptic membrane?
A
- 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
Q
What is electron microscopy?
A
- allows us to see small anatomical structures such as synaptic vesicles
32
Q
The diameter of things
A
0.001 mm - 1 micron (um) = 1000 nanometers (nm)
- small synaptic vesicle: 30 nm
- typical protein: 3 nm
- mitochondria: 1 um
33
Q
small synaptic vesicle
A
- job to breakdown neurotransmitter
- can hold 5000 molecules
34
Q
What is a ligand?
A
- a signalling molecule that binds to a receptor
35
Q
What are ligand receptor interactions?
A
- signalling within and between cells
36
Q
What are the 2 categories of neurotransmitter receptors?
A
- ionotropic receptors
- metabotropic receptors
37
Q
What is a binding site?
A
- place on a receptor where a ligand binds
38
Q
What is an ionotropic receptor?
A
- 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
Q
What is a metabotropic receptor?
A
- 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
Q
What are intracellular receptors?
A
- receptors located inside the cell
41
Q
What are surface receptors?
A
- receptors located on the cell membrane
42
Q
What are the 2 types of surface receptors?
A
- postsynaptic receptors
- presynaptic receptors
- extrasynaptic receptors
43
Q
What is a postsynaptic receptor?
A
- receptor located on postsynaptic membrane
- Can be ionotropic or metabotropic (most synapses contain both)
44
Q
What is a presynaptic receptor?
A
- receptor located on presynaptic membrane
45
Q
What is a extrasynaptic receptor?
A
- receptor located near but outside a synapse
46
Q
How is neurotransmitter signalling in the synapse kept brief?
A
- diffusion
- enzymatic deactivation
- reuptake
They stop neurotransmitters from reaching the end of the synapse or clear them away they do
47
Q
What is diffusion?
A
- Passive movement from areas of high concentration to areas of low concentration
- always happening
- some neurotransmitters leave synapse and float away
48
Q
What is enzymatic deactivation?
A
- Destruction of a neurotransmitter by an enzyme
- put protein in synapse to break down neurotransmitters
49
Q
What is reuptake?
A
- Reuptake transporters recycle neurotransmitters by pulling them back into the cell that just released them
50
Q
What is postsynaptic potential?
A
- 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
Q
What is a fast postsynaptic potential?
A
- Ionotropic receptors produce rapid postsynaptic potentials (1 to 5 ms)
52
Q
What is a slow postsynaptic potential?
A
- Metabotropic receptors do not always produce postsynaptic potentials, but when they do, they are relatively slow/delayed (~100ms to 10s)
53
Q
What is an excitatory postsynaptic potential?
A
- EPSP
- the result of positive sodium ions entering the postsynaptic cell, causing membrane depolarization and perhaps an action potential
54
Q
What is an inhibitory postsynaptic potential?
A
- IPSP
- the result of negative chloride ions entering the cell, causing membrane hyperpolarization and fewer action potentials
55
Q
What is depolarization?
A
- 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
Q
What is hyperpolarization?
A
- 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
Q
Are ionotropic receptors excitatory or inhibitory?
A
- classified as excitatory or inhibitory based on whether they let in Na+ or Cl- ions and thus cause EPSPs or IPSPs
58
Q
Are metabotropic receptors excitatory or inhibitory?
A
- 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
Q
How does a membrane depolarize?
A
- Sodium ions must enter the cell at a faster rate than potassium ions leave
60
Q
What is neural integration?
A
- 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
Q
What determines if a neurotransmitter is excitatory or inhibitory?
A
- 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
Q
How does the neural circuit work?
A
- 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
Q
What’s the difference between neural and behavioural excitation?
A
- 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
Q
What is a receptor protein?
A
- 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
Q
What is an ionotropic receptor?
A
- 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
Q
What is a metabotropic receptor?
A
- 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
Q
What cellular processes can metabotropic receptors affect?
A
- opening ion channels
- changing gene expression
- secretion of substances
- cell growth
- cell division (not in neurons)
- cell death
- anything the cell wants
68
Q
What is a g protein?
A
- 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
Q
What is the activation cycle of g proteins?
A
- 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
Q
What are g protein gated ion channels?
A
- ion channels that are gated by g proteins
71
Q
How is a g protein gated ion channel opened?
A
- 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
Q
Where can synapses form?
A
- 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
Q
What are axoaxonic synapses?
A
- 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
Q
What is presynaptic inhibition?
A
- 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
Q
What is presynaptic facilitation?
A
- 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
Q
What is an autoreceptor?
A
- 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
Q
What is a postsynaptic receptor?
A
- receptor located on the receiving neuron
