Lecture - Physiol 3 Synaptic Transmission

Question 1

What is RMP highly sensitive to?

Answer 1

Concentration of K+ extracellularly

Question 2

What happens in a migraine?

What happens in infarct?

Answer 2

1. What happens in a migraine = wave of depol passing through brain

Cells become hyperactive for some reason and polluting own environemnt by releasing K - opening K channels since been v active to make them repolarise so extracellular K increses that depolarise neighbouring neurons and they will enter AP generation and release K - this wave of excitation passes through cortex at a fixed rate (3mm/min) which is a wave of extracellular potassium and it drives neurons into high levels of activity and maintains them in a depolarised state such that they stop and shut down. That’s why he gets a hole in visual feild after this wave passes.

Basically, small change in extracellular K can have profound effect in the mem pot - can’t maintain mem pot if deviations in extracellular K.

2. Here is a profound example of inadequate perfusion - it’s an infarct. Penumbra around the dead tissue (those cells in dead tissue would have depolairsed and fired dramatically and then just died as a result of not having adequte nutirients to bring potential back down - Ca entereed and signalled apoptosis). The area around the dead tissue is an area of compromised circulation (red has less compromised circulation). So around the boundary of dead and orange, you have cells that are exposed ot high Ca levels - depolarises them and starts to generate activity and they are in the orange area and they can’t cope with the high levels of the inactivity. SO these waves of K and depol and high level of neuronal activity pass out through the tissue and this gives the neurological decline following a stroke. The more activity you force these neurons to undergo, the more likely it is that they won’t survive.

Question 3

Propagation of AP

1. How does it happen in unmyelinated axons?
2. K+ channels operate slowly - why?
3. Propagation is normally in one direction only - why?
4. What determines conduction velocity?

Answer 3

1. There is continuous conduction. If measure a little further away from the depol site, it’s approaching peak - but some charge is getting stuck or lost but some can affect neighbouring channels
2. These channels operate more slowly so they dont complete with Na channels and dont interefere with reaching peak. They have the same stimulus etc as Na
3. Bc behind is the inactive yet open channels and they cant get activated
4. Myelin

Question 4

What are factors determining conduction velocity (myelin not introduced yet)

Answer 4

Conduction velocity depends on how long it takes to generate an action potential at B, 􀀁following an action potential at A (m/s)􀀁

This depends on how fast charge build-up occurs at B, to bring membrane to AP threshold􀀁

This depends on the proportion of charge that flows along the axon (current in axoplasm), versus
t􀀁hat leaking out or trapped in membrane capacitance

So like, some charge lost in capacitance, some leaks and little gets further

Question 5

What three things can you do to increase conduction velocity?

Answer 5

• reduce resistance to flow along axon (increase diameter)􀀁
• reduce membrane capacitance􀀁
• reduce leak (increase membrane resistance)

Question 6

So there are two strategies to increase conduction velocity - one is to increase diameter, another is to have myelin. Discuss these two

Answer 6

Increasing diameter:

• Reduce resistance to flow along axon
• Proportionally, more charge flows along axon
• Position “B” gets to threshold more quickly
• But this has physical limitations; we have too many axons and can’t make them all huge

Myelination:

• Few channels under myelin, less leak
• Proportionally more charge flows within axon
• “B” gets to threshold more quickly
• There is less capacitance - greater charge separation (This fatty insulation - decreases capacitance. Capicitor is just an insulator seprating two conductors. If make separation bigger (myelinate) then the charges on either side can’t interact nearly as much so reduces the ability for charge to be stored across membrane)

Question 7

What’s the role of nodes of Ranvier?

Answer 7

Even with myelin, still some leak and capacitance. Action potential beginning at “A” will die out before end of nerve, if not regenerated. Nodes of Ranvier solve this problem:

• Nodes are spaced so that potential still above threshold for AP (Enough charge can get from A to next node to generate AP at next node)
• Nodes contain voltage gated channels, support new A.P.(“saltatory” conduction)􀀁
• A.P. at each node is the same; AP at end of axon is the same size as at beginning

In my words:
No AP being generated under myelin - just charge flowing inside the axon. Just confuction of charge leading to propagation. Each node of ranvier charges up to get charge to next node to create AP again. Takes v little time for charge to get from node to node. So conduction velocity much higher.

Question 8

Consequences of axon demyelination?

Answer 8

e.g. Guillain-Barré, multiple schlerosis, trauma

In the part where there is no myeline (where it’s meant to be): doesnt have expression of Na or K channels so this part isnt capable of generating AP itself. Dont get propagation so get conduction failure after this injury. So yeah, fewer vg channels in demyelinated regions so get conduction block - potential from previous node decays to below threshold at next intact node

So you’ll increase capacitance, increase leak, decrease conduction velocity (takes longer to get to next intact node to threshold)

Question 9

The chemical synapse:

1. How is information passed between excitable cells?
2. Which neurotransmission allows more sophisticated processing?
3. Chemical neurotransmission involves movement of what between cells?
4. These transmitters are important targets for what?

Answer 9

1. Information passes between excitable cells via synapses􀀁
   • ELECTRICAL (gap junction)􀀁 - Current can flow from one cell to another through pores - can be found in dendrites or something but there is chemical communication more in the brain
   • CHEMICAL - do more things like adjust expression of receptor etc
2. Chemical neurotransmission allows more sophisticated processing
3. Involves movement of neurotransmitters between cells
4. Important targets for therapeutic drug action……􀀁
   e. g. serotonin uptake blockers in depression, AChesterase inhibitors in MG􀀁

Question 10

Chemical synapse

Explain it

• activation of transmitter release
• synaptic transmission
• termination of transmission

Answer 10

So you have the pre-synaptic and post-synaptic axons. The AP comes to the terminal bouton. This depolarisation (if enough - usually is) opens the voltage-gated Ca channels. Ca comes in and causes the vesicles (which contain neurotransmitters) to fuse with the membrane and release their contents. The neurotransmitters then bind to the transmitter receptors (which can be directly or indirectly gated).

For the termination - intracellular Ca is pumped out with the Ca pump. For the vesicular fusion, only need small amount of Ca. So the pumping is important.

Vesicular membrane also recycled bc dont want terminal to increase in SA - need to not let it expand so get pinocytosis back into pre-synaptic bouton

1. Diffusion - just let the neurotransmitter diffuse
2. Enzymes (NMJ basement membrane, products taken up by terminal): like Ach-esterase. Can go into BS and get broken down by an enzyme in circulation
3. Re-uptake: Can even work on intact neurotransmitter (just take it back up) but pieces can be taken up after they are broken down by idk an enzyme

Can control rate of synthesis and expression of pump so terminals are also sensitive to pre-synaptic thing

Neurotransmitter released by post-synpatic cell too to change the receptor or whatever