Lecture 5- AP and AIS Flashcards
1
Q
What are the characteristics of an AP?
A
- usually need multiple inputs summated to generate an AP
- need to contrast between the graded potential and the AP
- once the membrane of the cell gets to the threshold= when the voltage gate ion channels open then all or none AP happens, the size is the same, the size doesn’t convey information
- on or off with APs, it is like digital, on off, the coding/ language is the pattern of the firing
- you get burst (calcium increase)
- slow firing will make the vesicles with glutamate and so on to release (low density vesicle) -high frequency then large dense vesicles released and peptides and modulators are involved
2
Q
What are passive/graded potentials, and their characteristics?
A
- passive potential that change the resting potential of the membrane, have the property when they deacy very quickly from where they are initiated, decay over parts of millimeters, so not good for long distance communication
- length constant of the membrane= determined there is a leake and resistance to the current,
- if you can increase the length constant then can change the distance the passive potential can travel
- myelinated axons have longer length constant as they do not have leaks
3
Q
Why do we need an AP?
A
- so we need sth like an AP to transmit over long distances
- from a point of generation, the AP maintains the size and pattern
- there is no limit to how far AP can travel as it is a regenerated process, so can go to the moon
4
Q
What happens to an AP as it travels along an axon?
A
- The action potential isn’t just bigger, it is actively regenerated as it moves along the axon.
- actively regenerated along the axon and that is why it can travel far
5
Q
What do we have to have to generate and AP?
A
- to induce an AP we have changes in conductance of Na and K, these underlie the development of the AP
- they line the membrane, like a wave along the axon
- depolarisation of the cell will lead to an interior change in its polarity
- hyperpolarisation and then goes back
6
Q
What is this?
A
- the conductance that you see through the K+ channels
- patch clamps recordings of single K+ channels
- when depolarized the channel opens and closes when cell goes to hyperpolarised, faithfully represents the state of the cell
7
Q
What is this?
A
- Na channels conductance -responding to the same voltage change as the K+, here opens, conducts and closes, goes to state of non-conductance
- stays in non conductance even tough the cell remains depolarised
- the inactive form is crucial
8
Q
What is the behaviour of Na+ and K+ channels upon reaching the threshold?
A
- in response to cell reaching threshold= large Na+ conductance (Na+ going in along chemical and electrical gradient)
- at the same time K+ channels open, initially there is little drive for the K+ but as the cell is more depolarized the gradient grows and the K+ moves restoring the cell to its state
9
Q
What happens to the Na+ channels upon reaching threshold?
A
- in response to depolarization, Na goes from closed to open, it has a little arm, and almost as soon as the channel opens the arm swings and blocks the entry of Na+
- the channel is in inactivated conformation
- only when cell goes back to hyper-polarized state then the arm moves and the channel goes to its closed confirmation
- the inactivated state is crucial to make sure that the AP only goes in one direction
- leads to absolute refractory period= the period when inactivated Na+ and cannot fire
10
Q
What is a relative refractory period?
A
-then period where the Na+ are ready to be open again, but because the cell is hyperpolarized must have bigger input to get an AP= this period is called a relative refractory period
11
Q
What is an absolute refractory period?
A
- when the Na+ channels are in their inactivated conformation and cannot open
12
Q
What does this show?
A
- there is a dissipation in the size of the graded potential, the further you are from the cell body the larger the potential must be to affect it
- how and where do we generate an AP?
- axon initial segment= the site where the AP is initiated and inputs are integrated
13
Q
How was it experimentally found that there is a specific site where AP is generated?
A
- bleb= when you cut an axon the sealage, larger and enables people to put a patch on it -can record membrane potential
- AP occurs earlier at the bleb than at the soma, called the axon initial segment
- AP more rapidly in axon then soma
- can go in both sides to the soma and to the other end to sent info
14
Q
Where is the axon initial segment?
A
- initial segment is between the hillock and the firs node of ranvier
- the soma starts to be invaded later
- don’t talk about the AP invading the soma and dendrites, it does happen particular in some cortical neurons,
15
Q
What does the axon initial segment look like and what does it do?
A
- the blue structures= inputs from other neurons onto the AIS
- AIS is not just site for initiation of APs but for modulation of the neuronal activity
17
Q
What special channels are concentrated in the AIS?
A
- we know that particular types of Na+ channels are concentrated at the AIS
- Na v 1.6 and Kv 1.2, detect it in the AIS but almost nothing in the soma
- the right pic= the dots look Nav 1.6
- particular types of Na+ channels congregate in the AIS
18
Q
What is the distribution of channels along the neuron?
A
-also calcium are concentrated in the AIS much more than in the soma, also at the node of ranvier where get the regenration of AP and different ones at the terminal where the vesicles are released
19
Q
How does the structure of Na+ channels differ from K+ channels?
A
- four different AA chains come together to make the K+ channel
- Na+ channel is only one AA chain, but it has subunits within it that have the same basic structure, 6 transmembrane spanning membrane and then again and again
- the long bit= alpha subunit
- then beta subunit= sensitivity, modulate the alpha subunit, not involved in the sensitigity or the pore -the main subunits on the diagram
- sensitivity to puffer fish tixin TTX,
23
Q
What does this show?
A
- comparison between Nav 1.2 and Nav 1.6
- express just one and then the other, so you can look at their voltage properties
- peak current graphs
- 1.6= peak current is greater than 1.2 so 1.6 lets in more Na and its sensitivity is greater, as you get change in -70/-60, at 1.2 no response till -40 = so causes the change in threshold sensitivity at the AIS as there is more 1.6
24
Q
What induces the localisation of certain ion channels in the AIS?
A
- why is Nav 1.6 concentrated at AIS, what makes it occur there
- the blue= just showing that it does occur
- the AIS= localization ANkG and NF186, AnkG= master controller of tge structure of the AIS, multiple proteins are linked to it= look at pick lower down -like NF186 etc.
- bind to AnkG= binds vitaB sohectrin= binds to the cytoskeleton
- there is something AnkG that means all the other components get concentrated there at the AIS
- at the node of ranvirer= there is also of collection of voltage ion channels, also llinked via AnkG!, here in the node= is brough there via interaction between axon membrane (myelin sheath) and the glial cell
- not sure what brings AnkG to the CNS -links everything to the axon skeleton and brings it to the right place
25
Q
What is the crucial protein at play with establishing the AIS channel density?
A
AnkG
