Lectures 9 & 10: Synapses Flashcards
1
Q
Synapse
A
- Site at which an impulse is transmitted from one cell to another
- Electrical and chemical synapses
2
Q
Electrical synapse
A
- Nervous system, some types of smooth muscle, cardiac muscle, embryonic cells, via gap junctions
- Each channel is hexagonal array of 6 subunits (a connexon)
- Each subunit is made of the protein connexin
3
Q
Chemical synapses
A
- Nervous system: presynaptic > postsynaptic neuron)
- Receptor cells > sensory neuron
- Motor neuron > muscle cell (the neuromuscular junction, NMJ)
4
Q
Characteristics of electrical synapses
A
- Continuous (2-5nm gap)
- Almost no synaptic delay
- Potential bi-directional transmission
- Coupling ratio (ratio of sizes of presynaptic and postsynaptic potentials) does vary (<50%)
- Not readily altered by pharmacological agents
- Connexon channels can be modulated
5
Q
Bi-directional transmission of electrical synapses
A
- Can allow passage of ions and larger molecules (cAMP, IP3)
- Rectification occurs in many places
- Mammalian CNS reflexes pathways, conduction may be bi- directional where you want very little delay or want a number of neurons to fire together (synchrony needed)
6
Q
Connexon channels are usually open, but can be closed by
A
- Increased [Ca]i or [H]i
- Depolarization of one cell
7
Q
When cell is coupled via gap junctions
A
- Channels provide a low resistance pathway (Rc) that is much lower than Rm
- Ions take pathway of least resistance
8
Q
In normal cells,
A
- No current flow, because of high rm and Ri
- Current flows away (path of least resistance) without entering next cell
9
Q
Chemical synapse characteristics
A
- Membranes of presynaptic cell separated by synaptic space from membrane of postsynaptic cell (20 – 50nm)
- Synaptic delay (0.5 msec)
- Conduction is one way, always forward (Bell-Magendie Law)
- Synapses on dendrites, axons, or cell body
10
Q
Chemical synapse mechanism
A
- Chemical substance released from presynaptic cell
- Interacts with membrane of postsynaptic cell
- Produces a change in its membrane permeability
- Results in an electrical or chemical response
11
Q
Action potential conduction to axon terminal
A
- Action potential not conducted along surface of axon terminal membrane
- Induces it to depolarize and open voltage-dependent calcium channels (N-type)
12
Q
Calcium enters the axon terminal
A
- Down its electrochemical gradient
13
Q
The increase in [Ca]i causes
A
- Synaptic vesicles to move and fuse with the surface membrane
- Open to release their chemicals (neurotransmitters) into the synaptic cleft
14
Q
An increase in [Ca]i is important for the release of many secretory substances from
A
- Cells of various types
15
Q
Released transmitter
A
- Diffuses across cleft to postsynaptic membrane that contains receptors
16
Q
Transmitters must bind to
A
- Specific receptor sites on postsynaptic membrane
- Amount of binding will be dependent on amount of transmitter released
17
Q
Neurotransmitter binding causes
A
- Opening of specific ion channels (for Na or K or Cl)
- Evoke a change in membrane potential (the postsynaptic potential/PSP)
18
Q
Neurotransmitter can be removed form synaptic cleft via
A
- Diffusion away (for all transmitters)
- Enzymatic destruction of transmitter molecule
- Reuptake of transmitter into terminal
19
Q
Neurotransmitter removal processes favor
A
- Unbinding
- Leads to restoration of Vm to resting level and termination of neurotransmission
20
Q
Enzymatic destruction of transmitter molecule occurs in
A
- Some molecules
- ACh
21
Q
Reuptake of transmitter into terminal
A
- Often a sodium dependent process
- Major for catecholamines
22
Q
Excitatory postsynaptic potentials (EPSPs)
A
- Chemical released when binding to postsynaptic membrane induces a non-selective increase in Pm to all small ions
23
Q
EPSP results in
A
- Depolarization since in resting membrane PK»>PNa
24
Q
An increase in PK, PCl, and PNa leads to
A
- Net movement of positive charges inside, hence depolarization
25
EPSP depolarizing response magnitude
- Small, around 1-2 mV
| - Decreases decrementally as EPSP moves away from synaptic region
26
A single EPSP
- Not large enough to reach an
action potential threshold
- Will take nerve membrane closer to threshold
- Summation will be required
27
Presynaptic neurons that cause EPSP's in postsynaptic cells are called
- Excitatory neurons
| - The neurotransmitter released is an excitatory neurotransmitter
28
Convergence is characteristic when
- Many presynaptic neurons synapse on one postsynaptic cell
| - These are the most common type and are the ones that allow integration
29
Divergence
- One neuron sends branches that synapse with many postsynaptic neurons
30
Motor neuron to Renshaw cell
- Divergent
| - One presynaptic action potential produces a burst of action potentials in many postsynaptic cells
31
Motor neuron to Renshaw cells are rare
- Renshaw cells in ventral horn inhibit monosynaptic reflexes (also group Ia inhibitory interneurons)
- Produce recurrent inhibition (or facilitation)
32
At one-to-one synapses, such as NMJ,
- There is no integration
33
Inhibitory postsynaptic potentials (IPSPs)
- Chemical release causes a selective change in membrane permeability to K and/or Cl
34
Increase in PK causes
- Hyperpolarization
| - The effect of increasing PCl depends on Vm relative to ECl
35
Usually Vm = ECl or Vm is a little less negative than ECl, so
- Net effect in the first case is to reduce the size of EPSP's if occurring
- Or in the second case to cause hyperpolarization
- In either case, inhibition results
36
A neuron that causes an IPSP is called
- Inhibitory neuron
| - Transmitter released is an inhibitory neurotransmitter
37
In some parts of the nervous system,
- A neurotransmitter can be excitatory
- In other parts inhibitory
- Also, more than one neurotransmitter may be released at a synapse
38
Presynaptic inhibition
- Depolarization-dependent neurotransmitter release
39
Lowered resting Vm leads to
- Reduced AP magnitude > less transmitter release at synapse > transmission inhibition/failure at “E”
40
All of the electrical signals are integrated along the membrane, but along the dendritic and nerve cell body membrane
- No action potentials are produced
41
Axon hillock membrane has lower action potential threshold so if depolarization is sufficient,
- An action potential will be generated and propagated
| - Transfers information further in the circuit
42
Modulation of calcium release
- Extracellular calcium (Cao) required for vesicle release
| - Removal of Cao abolishes vesicle release
43
Increase in [Mgo]
- Also reduces the number of vesicles released
| - Competes with Ca
44
Increase in [Cao] or a decrease in [Mgo]
- Increases release of vesicles
45
Synaptic transmission can be modified by
- Alterations in plasma [Ca] or [Mg]
46
Fatigue (depression) of synaptic neurotransmitter release occurs upon
- Repeated stimuli
47
Botulinus toxin
- Reduces ACh release at synapses, especially at NMJ
48
Facilitation
- Increase in amount released (short time span)
| - Post-tetanic potentiation is another form of augmentation
49
By presynaptic inhibition
- Reduces the amount of transmitter released
50
Long term potentiation involves
- Protein synthesis
| - Perhaps involved in memory
51
Acetylcholine (ACh)
- Found in both peripheral and central nervous system
- Betz cells of cortex
- Basal ganglia and movement control, senile dementia (Alzheimer's) involves cholinergic pathways
52
Catecholamines
- Epi/Norepinephrine in peripheral, also central nervous system
- Dopamine synapses lost in Parkinsonism
- Overactive dopamine implicated in certain psychoses
53
Excitatory
- Glutamate and aspartate
| - Serotonin involved in thermoregulation, mood, behavior
54
Inhibitory
- Glycine
| - GABA
55
General anesthesia
- Prolongs open time of GABA receptors-linked chloride channels
- Leads to prolonged postsynaptic inhibition at GABA synapses
- GABA synapses are a major target of general anesthetic
56
Nitric oxide (NO)
- Gaseous
- Not packaged and released from vesicles
- Short-lived
- Produced as needed
57
Nitric oxide (NO) found in
- Enteric nervous system
- Certain blood vessels
- Skeletal muscle
58
Some neurotransmitters (peptides) are made by
- Nerve cell under control of the nucleus of the nerve cell
- These neurotransmitters made on ER, packaged by the Golgi and conducted to axon terminal by a fast axoplasmic transport system
- Others may be synthesized in the terminal
59
Depolarization causes
- Release of number of vesicles
| - Each vesicle contains a certain amount of molecules
60
The amount/per vesicle
- Quanta
61
Besides the basic, more classical neurotransmitters, certain neurons contain
- Small neuropeptides
| - Act at low concentration to excite or inhibit other neurons
62
Neuroactive peptides
- Range from two amino acids to about 40 amino acids long
63
Some neuroactive peptides may act as neuromodulators
- Modifying the release or effect of a neurotransmitter
64
Pre-synaptic events
- Arrival of action potential at terminal
- Opening of voltage-gated Ca channels
- Ca entry into terminal
- Triggering of SNARE proteins > vesicle release
- Diffusion of NT across synaptic cleft
65
Post-synaptic events
- NT binds to receptors on post-synaptic membrane
- Opening of ion-specific channels > change in membrane permeability > change in Vm
- Change in Vm = Post-synaptic potential (PSP)
