1.3 Signal Propagation, Transmission and Integration Flashcards
Lecture 3
1
Q
After injecting current into cells what happens to the associated membrane potential
A
the potential changed show transient, non-linear rising phases as well as a plateau
2
Q
plotting the plateau membrane potential (Vm) against the injected current gives a β¦
A
linear relationship and obeys Ohmβs law
V = IRin
3
Q
What is Rin
A
neurons input resistance and depends on Rm normalised for SA
4
Q
What does Rm depend on
A
distribution of ion channels
5
Q
Equation for Rin
A
Rm/4(pi)(a^2)
6
Q
What does injecting current in to a cell do
A
induces a voltage change in time which is caused by an outward current across the membrane (Im)
7
Q
equation for Im
A
Im = Ii + Ic
8
Q
what is Ii
A
current across Rin
9
Q
what Ic
A
current discharging the membrane capacity Cm
10
Q
what is the equation to the rate of change of the membrane potential
A
π«π½π(π) = π°ππΉππ (π β (π^(β(π/ π)))
11
Q
what gives the palteau value
A
ImRin
12
Q
what affects the rate of change
A
exponent -π/ π
13
Q
what does it mean if π‘ = π
A
63% of max voltage reached
14
Q
what is π
A
π = π πππΆπ
15
Q
how to find the total current flow
A
sum of fast transient Ic discharging/charging Cm and slowly building up Ii through Rin
16
Q
why is there a leakage current
A
originally we assumed isotropic potential distribution but the membrane is not
a perfect insulator so there will be a leaky current whenever voltage change occurs
17
Q
how does local voltage changes propagate along different parts of the cell
A
it depends on the ration between the membrane resistance (rm) and the longitudinal resistance along the axon (ra)
18
Q
what is ra
A
result of the fact that ion-based current in the axon is less efficient as electrons flow in a copper cable
19
Q
how can passive properties of an axon be modelled
A
by assuming distinct compartments connected by the axonal resistance
20
Q
what is the voltage change spreads along the axon
A
Ξπ(π₯) = Ξπo.π^(β π₯/ π)
π = β(ππ/ππ)
21
Q
what does lambda mean
A
indicates the distance from the initial voltage change at which the membrane potential drops to 37%
22
Q
efficiency of electronic conduction influencesβ¦
A
spatial summation in triggering synaptic potentials as well as the propagation of AP
23
Q
What is a factor in the propagation of AP
A
electronic conduction
- once the membrane at any point on the axon reaches threshold depolarisation an AP is generated in that region
- local depolarisation spreads passively causing successive adjacent regions to reach the threshold and generate an AP
24
Q
What happens when AP propagrates from right to left?
A
causes a difference in membrane potential in 2 adjacent regions of the axon and the difference creastes a local circuit causing the depolarisation to spread passively
25
what happens when depolarisation spreads passively
current spreads from the more positive region to the less positive resting region ahead of the action potential so to the left as the AP travelling right to left as well asto the less positive area behind the action potential so towards the right
26
what happens, with regards to the AP, due to an increase in membrane K+ conductance in the wake of an AP
the buildup of positive charge along the inner side of the membrane towards the right will be more balanced by the local efflux of K+ allowing the region to repolarise
27
What happens a short time later after the first AP
the AP will trave; down the axon and process will repeat
28
what happens to axons with longer length constants (lambda)
they have local currents that spread a greater distance down the axon so AP propagates more rapidly
29
is passive spread of depolarisation instantaneous
no, electronic conduction is rate limiting factor in propagation
30
what happens with AP in a section depolarises current to adjacent membrane
causes gradual depolarisation to threshold
| - larger ra the smaller the current and the slower the propagation
31
what speeds up AP propagation
increasing lambda by increasing rm
| - done by patches of myelin sheaths (addtional insulation) along axons (increasing rm so increases lambda)
32
gain in propagation speed due to...
AP generation takes longer that passive electrotonic conduction of voltages along axon
33
is signal propagation faster as internodes or nodes of Ranvier
faster at internodes
34
increases speed about...
10x
35
what are the 4 properties important for neuronal signalling with AP
1. Threshold for initation
2. All or nothing event
3. self - regenerative
4. refractory period
36
whats threshold for initiation
as depolarising current increases, ππ β β50 ππ
37
whats all or nothing event
AP stereotyped regardless of amount past threshold
38
what self-regenerative
Can be conducted over great distances
39
whats the refractory period
Limits frequency of signals
40
whats responsible for the rising phase of the AP
Na+ influx
- depolarisation of the cell past threshold causes increase in Pna which overwhelms the dominant resting Pk which drives ππ β πΈππ
41
the falling phase is due to...
β ππΎ
42
whys it difficult to measure Na and K conductance as function of Vm
due to the strong interdependence between membrane potential and Na+/K+-VGCs due to the +ve feedback nature of AP generation
43
why does the voltage-clamp technique make measuring the conductance
it interrupts this interdependence by adding/withdrawing current from the axon equal to the current flowing through VGCs
This prevents ππ from changing
The amount of current needed to prevent this change is a direct measure of current flowing across the membrane
44
how to analyse the current waveform in more detail
by applying the pharmacological drugs
45
how to reveal the contribution of potassium current
An ion channel blocker of the Sodium channels, tetrodotoxin (TTX)
46
how to show the sodium current
Tetraethylammoniom (TEA), which blocks the Potassium channels
47
what determines the size of Na and K currents
2 factors:
- magnitude of the conductance which reflects the number of channels open for each species
- the electrochemical driving force
πΌnπ = πnπ Γ (ππ β πΈnπ) πππ πΌk = ππ Γ (ππ β πΈπ)
48
what are the voltage gated ion channels three states
- closed activatable
- open
- closed inactivatable
49
what do ion channels achieve
variable conductances
50
What happens with ion channels if at resting Vm?
| 1st part
The channels are closed
- membrane capacity is discharged and threshold potential is reached
- "activation gate" opens
- Na+ flux initiated
51
What happens when activation gate open?
| 2nd part
causes further depolarisation due to Na flux
| more VGC are opened
52
how is the channel inactivated
after a short period it gets inactivated by means of a slow "inactivation gate"
(ball and chain hypothesis so channel gets blocked)
53
what happens if the membrane potential drops below the threshold
"the inactivation gate" is replaced with the "activation gate" in the closed position
54
what happens when there is a depolarisation of the membrane beyond the threshold (-50mV)
β πππ as ππ+-VGCs open rapidly
| Inward ππ+ current
55
what causes further depolarisation (AP stuff)
membrane capacitance discharged causes it
- Positive feedback causes more ππ+-VGCs to open
- Increase in inward ππ+ current
- Regenerative process drives ππ β πΈππ
- This is the rising phase of the AP
56
what happens when Na channels gradually inactivate and K channels open
K channels opens with a delay (delayed rectifier)
β πππ and β ππ
- Outward πΎ+ current tends to repolarise the membrane
57
what happens when hyperpolarisation occurs
ππ depolarises past resting potential
- πΎ+-VGCs take time to close so ππΎ > ππ,πππ π‘πππ for a few ms
- ππ is closer to πΈπ
58
whats the absolute refractory period
Impossible to fire another AP as all ππ+-VGCs inactivated
59
what causes the relative refractory period to be entered
As some πΎ+ channels close and ππ+ channels recover from inactivation the relative refractory period is entered
Stimuli greater than threshold triggers AP
60
What is the patch clamp experiment
A specialised glass micropipette with a tight seal between it and the membrane allows the recording of current through a single channel
o Allows understanding of properties of ionchannel molecules
o Demonstrate that VGC have two conductance states: open and closed
61
What does the patch clamp show as a result of depolarisation
a channel opens in allor-none fashion
o Brief current pulses of variable duration but constant amplitude
o Rapidly terminated by inactivation
ο· Averaging over many channels gives the same result as voltage-clamp experiments
62
whats a synapse
site at which one neuron communicates with another
63
what are the 2 forms of synaptic transmission
electrical or chemical
64
what does cellular activity do to the strength of a synapse
enhance or reduce
65
what are electrical synapses used for
used to send rapid, stereotyped depolarising signals
66
what are chemical synapses uses for
capable of more varying signalling
o Can produce more complex behaviours
o Mediate excitatory or inhibitory actions in postsynaptic cells
o Produces electrical changes of varying durations
o Amplify neuronal signals
67
First part of electrical synapses
ion channels in presynaptic cell generates a current that depolarises the postsynaptic cell
presynaptic terminal has to be big enough to contain many channels to generate a large enough current
postsynaptic cell must be smaller so Rin is larger and Ξπ greater
68
Second part of electrical synapses
| depolarising and hyperpolarising currents
Depolarising and hyperpolarising currents can be transmitted
o Similar to passive propagation of sub-threshold electrical signals along axon (aka electrotonic transmission)
o Some synapses have VGCs that permit unidirectional transmission (rectifying synapses)
69
Third part of electrical synapses (gap junction)
transmission happens through region called the gap junction which is about 20 nm and is bridged by gap junction channel proteins
70
what are gap junction channel proteins
- arranged in arrays
- conduct the ion current
- conformational changes in these channels can modulate conductance
71
How do chemical synapses work
nothing with structural continuity of pre and post synapse
chemical transmission depends on diffusion of neurotransmitter
- NS binds to receptors in post-synaptic membrane
72
size of synaptic cleft
winder than normal intercellular space (20-40 nm)
73
First part of chemical synapses (pre)
Transmitter is released from the presynaptic terminals
o These contain hundreds of synaptic vesicles with thousands of NS molecules each
o Clustered specialised regions called active zones
74
what happens during the presynaptic AP (chem synapse)
πΆπ2+-VGCs open causing calcium influx
o This causes fusion of the vesicles with membrane in exocytosis and release of NS into synaptic cleft
o Diffusion across cleft and binding with postsynaptic receptors cause opening of ion channels and altering of membrane potential and conductances
ο· This process takes time so a delay is introduced (>0.3 ms)
75
where can amplification occur (chem syn)
it can occur as each synaptic vescile contains thousands of NS molecules
76
2 ways neurotransmitters control the opening of ion channels in the post-syn cell
directly (ionotropic) or indirectly (metabotropic).
| These two classes of transmitter actions are mediated by receptor proteins derived from different gene families.
77
what is direct gating
5 subunits each which has 4 membrane spanning alpha helix regions
78
What is indirect gating
receptors composed of single subunit with 7 membrane-spanning alpha helical regions that bind the ligand to membrane
receptors activate GTP - binding protein (G protein)
this activates a second messenger cascade that modulates the channel activity
G protein stimulates adenlyl cyclase converting ATP to cAMP
cAMP activates cAMP-dependent protein kinase (PKA) which phosphorylates the channels (P) changing the function
79
what do central neurons receive
receive both excitatory and inhibitory inputs and respond to a range of neurotransmitters through both ionotropic and metabotropic receptors
o These diverse inputs must be integrated
80
Type 1 of morphological types
Type 1: Glutamatergic
o Excitatory
o Contact at dendrites
81
Type 2 of morphological types
Type 2: GABAergic
o Inhibitory
o Contact at soma
82
what is the process of neural integration
Neurons integrate the various signals they receive into a single output
ο· Synaptic potential produced by a single presynaptic potential are not large enough to depolarise a postsynaptic cell to AP threshold
o The net effect of the inputs will depend on several factors: the location, size, and shape of the synapse, the proximity and relative strength of other synergistic or antagonistic synapses, and the resting potential of the cell.
83
What is the trigger zone
the axon hillock at the somatic base of the axon has a lower threshold for AP generation due to a higher density of ππ+-VGCs
84
whats does neuronal intyergration involve
summing the synaptic potentials that spread to the trigger zone and is critically affected by 2 passive membrane properties of the neuron
85
whats the membrane time constant
π: determines the time course of the synaptic potential and so controls temporal summation
ο§ The greater π the greater the likelihood two consecutive signals will summate to bring ππ to threshold
86
what is the length constant of the cell
π: determines degree of local depolarisation by passive spreading and so affect spatial summation
ο§ Longer π, more minimal decrement of signal
