WEEK7 - module 3. The Action Potential

 

Learning objectives

Be able to draw and/or label the typical action potential (AP) curve of mV vs time, indicating all of the following
•    RMP
•    Subthreshold potentials
•    Depolarization
•    Repolarization
•    Hyperpolarization
And be able to explain all the above in terms or sodium and potassium channels

 

Explain the “all or nothing” principle of AP propagation, and the role summation plays in AP propogation

 

Differentiate between slow and fast nerve transmission and role of myelin sheaths in this context.

 

Understand the basic pathology the underlies multiple sclerosis

It is an autoimmune system disease that our cell destroys the myelin sheath in the axon.

It prevents the saltatory conduction. 

The rate of signalling becomes so slow that it can cause tremor, a...

 

Understand how the common local anaesthetic Lignocaine works

 

 

 

 

 

 

PPT

https://www.youtube.com/watch?v=oa6rvUJlg7o 

*A bundle of axons traveling together is called a nerve
*The resting membrane potential is the point where the cell has achieved electrochemical equilibrium. This means that the concentration gradient and the electro gradient for each ion is equal and opposite.
*Ion channel-> ions move along their concentration gradient (passive diffusion)
: Voltage gated channel (electrically stimulated)only open when the membrane potential reaches a certain value
: Ligand-gated ion channels(chemically gated/ receptor mediated) are triggered to open when they are bound by a specific molecule 
: Mechanically gated ion channel is open in response to physical forces, such as changes in length or changes in pressure

*GRADED POTENTIAL 
-resulting change in membrane potential is small 
-vary in size
-can be positive and negative

*ACTION POTENTIAL
—70mv~threshold voltage of -55mV triggers the action potential at the axon hillock, which then travels down the axon

*VOLTAGE GATED SODIUM CHANNEL
1. Open 
2.closed (at rest)
3.inactivated

*ACTION POTENTIAL
1. Once the cell membrane reaches the threshold voltage, the channel changes to an open position and sodium rushes into the cell because of the electrochemical gradient
2. 0 mV = depolarisation
3. 0mV~+30mV = overshoot
4.As the membrane potential becomes positive, the sodium channel inactivation gate shuts. 
5.The voltage gated potassium channels open 
Because of the electrochemical gradient, potassium ions flow out of the cell, making it less positive and eventually negative = repolarisation 
6.Because the potassium channel is a little slow to close, for a  brief period, the membrane potential is hyperpolarized = hyperpolarization 
(More negative than resting membrane potential, during hyper polarised potassium channel closed)


*ABSOLUTE REFRACTORY PERIOD
During DEPOLARISATION, the inactivated sodium channels won’t respond to any stimulus at all.
During this time, the neuron is in its absolute refractory period, the period of time when a nerve cannot fire another action potential, no matter how strongly it’s stimulated. 
The absolute refractory period prevents action potentials from happening again too quickly and prevents action potential from traveling backwards along the axon.

*RELATIVE REFRACTORY PERIOD
During HYPERPOLARIZATION, the sodium channels are closed, and the inactivation gate opens. There’s no change in sodium flow but now they could be opened again. Because, while the sodium channels could open, it would take a larger than usual stimulus to reach threshold. Because the cell is hyperpolarised due to the potassium still leaving the cell

 

 

 

 

 

Changing the RMP

Types of Channels

*What might cause a mechanically gated channel to open?

Mechanically gated channels - open and close in response to mechanical vibration or pressure, such as sound waves or the pressure of touch (found in sensory receptors in the skin, ear, etc.); involved in generating graded potentials.

 

 

Graded and Action Potentials

*Why are action potentials self propagating but graded potentials not?

Action potential is generated and transmitted by the voltage gated channel. 

When the ions flows inside and outside, the membrane potential changes and it stimulate the surrounding channels. The channels open in turn like a dominoes and this helps the action potential self propagate. 

However graded potential is made by chemically gated channel or mechanically gated channel. 

They are only open when there's specific chemical compound or the mechanical force is existing.

When they are gone, the channel is closed, the membrane potential changes back to the RMP and there's no longer potential generated.

 

 

 

 

 

 

 

 

The Action Potential

*What would happen if there were Na+ channels in the membrane that were opened? How might this change the membrane potential?

*What is the significance of -55mV? Can you work out what the significance of -55mV is ?

*How many gates does this channel have?

Can you see what has activated (opened) the channel?

How many different states does the channel have?

 

*Cold slows all reactions, and can also be used to help anasethetise tissue- when it is used?

https://www.youtube.com/watch?v=5rFwzi4-oLo 

*What value might the hyperpolarisation approach?

Can you see that the hyperpolarisation gives rise to another refractory period. What is its name and what does this mean?

 

Na+ channel has inactivation and activation gate.

In RMP, Na+ activation gate is closed. When there's stimulus to the cell membrane, Na+ activation gate is open and the cell is depolarised up to 30mV by Na+ entering the cell. 

When the membrane potential hits 30mV (overshoot), K+ channel opens and K+ starts to efflux. It makes membrane potential negative, which is called repolarisation.

At the end of the repolarisation, K+ channel closes so slowly that K+ still efflux during the closing of the channel and it makes membrane potential more negative than RMP which is called hyperpolarisation. 

 

During the absolute refractory period, no more action potential is generated. It helps the direction of AP is only one way and no AP to be generated at the same time in the same point.

 

Relative refractory period is when K+ channel is still open and the Na+ inactivation gate is closed.

In this period, gate of Na+ channel reset to its original position same as RMP. (inactivation gate is open and the activation gate is closed) 

In this period, action potential can be generated but the larger stimulus is needed because the stimulus needs to compensate the negative polarity in the membrane potential which is caused by K+ efflux.

 

 

 

 

 

*Since the size/amplitude of an action potential does not change, how might your nervous system respond to increasing stimuli strength? 

*What role does the Na+/K+ ATPases pump here?

Lethal injection

*Why is high K+ in the ECF lethal? The plot on the left hand side should give you a clue

The concentration of K+ is important in maintaing Resting membrane Potential. 

RMP allows many functions in our body by helping delivering some signals.

K+ concentration is higher in ICF than ECF in RMP. If the K+ concentration is higher in ECF, K+ cannot diffuse out of the cell via the chemical gradient and it interrupts generating action potential or maintaining RMP.  This can cause many disfunction in our body, such as cardiac arrhythmias, muscle weakness, or paralysis.

 

 

 

 

 

 

Conduction Velocity

 

 

 

 

 

 

Multiple sclerosis

https://www.youtube.com/watch?v=qgySDmRRzxY&list=PL95B2C06957B8DEC1 

 

 

 

 

 

 

 

 

 

 

Self-paced quiz

 

 

 

 

 

SUMMARY

 

*How an AP is produced

 

*Why it is unidirectional

Unlike graded potentials, the propogation of an action potential is unidirectional, because the absolute refractory period prevents the initiation of an AP in a region of membrane that has just produced an AP.

 

*What limits the speed of firing

After the neuron has fired, there is a refractory period in which another action potential is not possible. The refractory period generally lasts one millisecond. During this time, the potassium channels reopen and the sodium channels close, gradually returning the neuron to its resting potential

 

*How a nerve can be made either more or less likely to fire an AP

 

*What myelination of axon achieves

 myelin sheath allows electrical impulses to transmit quickly and efficiently along the nerve cells

 

*Crucial significance of threshold potentials

threshold potentials are necessary to regulate and propagate signaling in both the central nervous system (CNS) and the peripheral nervous system (PNS).

 

 

*Three states of the Na+ channels, and how these affect AP frequency

1. Closed resting state -> RMP 

2. Open conducting state -> From threshold to peak potential (Depolarization)

3. Nonconducting inactivated state -> From peak to resting potential

Voltage-gated sodium channels open (activate) when the membrane is depolarized and close on repolarization (deactivate) but also on continuing depolarization by a process termed inactivation, which leaves the channel refractory, i.e., unable to open again for a period of time.

Voltage-gated Na+ channels have two gates: an activation gate and an inactivation gate. The activation gate opens quickly when the membrane is depolarized, and allows Na+ to enter. However, the same change in membrane potential also causes the inactivation gate to close. The closure of the inactivation gate is slower than the opening of the activation gate. As a result, the channel is open for a very brief time (from the opening of the activation gate to the closure of the inactivation gate).

Another important characteristic of the sodium channel inactivation process is that the inactivation gate will not reopen until the membrane potential returns to the original resting membrane potential level. Therefore, it is not possible for the sodium channels to open again without first repolarizing the nerve fiber.

 

 

*absolute refractory period & relative refractory period, and why they occur