Lecture 17 - The action potential

Question 1

Action potential

Answer 1

Action potentials are the basis of all neuronal communication - they are the electrical impulses

Question 2

Resting membrane potential

Answer 2

There is a charged separation between K+ and Na+. This charge separation across the membrane creates a voltage difference where the cell is said to be, by convention, inside negative in relation to the outside and this is called the resting membrane potential. The resting membrane potential in living cells is about -70mV. At rest, there are relatively more sodium ions outside and more potassium ions inside the cell.

Negative because you are using energy at the sodium potassium pump, ATP is being spilt into ADP and Pi at the pump. The cell is always busily swapping K+ and Na+, to keep sodium high outside the cell and to keep potassium high inside the cell so you are using energy to establish and maintain these concentration gradients and in doing so you have a negative inside in relation to the outside.

Question 3

Na+ and K+ inside and outside the cell levels

Answer 3

ECF = high Na+ and low K+ 
ICF = High K+ and low Na+

Question 4

Na+ gradient in a cell and what would happen if the cell membrane became permeable to Na+?

Answer 4

We have a concentration gradient for the movement of sodium, high concentration outside and low concentration inside the cell, so if the membrane were to become permeable, then it would suddenly allow sodium from the outside go inside. Sodium is positively charged and the inside of the cell is negative, opposite charges attract so if the channel was to suddenly open we would have a concentration and electrical gradient. Electrochemical gradient would, if the cell membrane was permeable, drive sodium into the cell carrying the positive charge with it. For sodium, the electrical and chemical gradients are inwards so if the membrane were to become permeable to sodium then there would be a very strong, rapid movement of positive charge into the cell

Question 5

K+ gradient in a cell and what would happen if the cell membrane became permeable to K+?

Answer 5

Potassium is high inside the cell and is low outside the cell. If the membrane were to be permeable to postassium, the potassium would move out of the cell carrying positive charge with it out of the cell but the inside of the cell is negative and the outside of the cell is positive so at rest the electrical gradient is into the cell for potassium. Could be confusing because the chemical gradient is outwards but the chemical gradient is inwards, at rest there is very little net gain or loss assuming that the membrane is permeable to potassium.

Question 6

Potassium chemical, electrical and electrochemical gradients

Answer 6

Chemical - Out of the cell
Electrical - Into the cell
Electrochemical - Out of the cell

Question 7

Sodium chemical, electrical and electrochemical gradients

Answer 7

Chemical - Into the cell
Electrical - Into the cell
Electrochemical - Into the cell

Question 8

Depolarisation

Answer 8

Depolarisation refers to a sudden change in membrane potential – usually from a (relatively) negative to positive internal charge. In response to this chemical stimulus, sodium channels open within the membrane.

Question 9

Repolarisation

Answer 9

Repolarisation refers to the restoration of a membrane potential following depolarisation (i.e. restoring a negative internal charge). Following an influx of sodium, potassium channels open within the membrane. The efflux of potassium causes the membrane potential to return to a more negative internal differential.

Caused as a result of the stimulus being removed and excess sodium ions being transported out of the cytosol

Question 10

Hyperpolarisation

Answer 10

Hyperpolarization is when the membrane potential becomes more negative. It is the opposite of depolarisation.

At this level the sodium channels begin to close and voltage gated potassium channels begin to open. After hyperpolarization the potassium channels close and the natural permeability of the neuron to sodium and potassium allows the return to resting membrane potential.

Question 11

What are action potentials sent through?

Answer 11

The axon of the neuron

Question 12

Where are the voltage gated Na+ channels and the voltage gated K+ channels located?

Answer 12

Found along the axon and at the synapse, voltage-gated ion channels directionally propagate electrical signals.

At the synapse are Ca2+ voltage-gated channels and on the axon are Na+ voltage-gated channels and K+ voltage-gated channels

The ones one the axon are important for propagating the information that is coded in an action potential from one end of the neuron to the other

Question 13

Voltage gated ion channels

Answer 13

Voltage-gated ion channels are a class of transmembrane proteins that form ion channels that are activated by changes in the electrical membrane potential near the channel. Found along the axon and at the synapse, voltage-gated ion channels directionally propagate electrical signals.

Nature has figured out that having two gates to make the timing of the opening and closing better is more beneficial

They are activated when the membrane potential change.

Question 14

How does a voltage gated ion open and close?

Answer 14

Channel closed - The activation get is closed therefore ions can’t get through even through the inactivation gate (closest to the cytosol) is open. The channel is closed at resting membrane potential

Channel opens - There is depolarisation of the membrane, the membrane becomes more positive. The gates open, the gates are actually part of the protein that gets influenced by the change in membrane potential and change shape, the channel itself changes ship and the gates open and as soon as the gate opens ions are able to travel in

Channel inactivated - More positive membrane potential. The channel starts to turn itself off, it closes its inactivation gate and the inactivation gate allows the channel to turn off very rapidly and eventually the acitivation gate will also close

Question 15

Steps for an action potential

Answer 15

At resting membrane potential the voltage gated channels are shut (there are a few leak channels open)

Step 1 - Depolarisation to threshold (intitial depolarisation/excitation that starts off the action potential - it triggers the action potential) = A local change in membrane potential occurs that is SUFFICIENT to depolarise the cell and open the voltage gate Na+ channels (about -60mV)

Step 2 - Activation of sodium ion channels and rapid depolarisation = voltage gated Na+ channels OPEN (about +10mV)

Step 3 - Inactivation of sodium ion channels and activation of potassium ion channels = The membrane rapidly depolarises and then the Na+ channels close and at the same time the voltage gated K+ channels open (K+ flows from outside the cell therefore the inside of the cell will start to become negative again (about +30mV)

Step 4 - Potassium ion channels close = Voltage gated K+ channels closes and the membrane depolarises to resting membrane potential (about -90mV)

Question 16

Where do most action potential originate?

Answer 16

Most action potentials originate near the axon hillock of the cell body in the initial segment of the axon and it then travels the length of the axon

Question 17

Absolute refractory period

Answer 17

Impossible to send another action potential

The inactivation gates of the sodium channels lock shut for a time after they have opened, so no sodium will pass through

No sodium = no depolarisation = no action potential

Question 18

Relative refractory period

Answer 18

During this time, it is really hard to send an action potential

This is the period of time after the absolute refectory period, when the inactivation gates are open again
However, the cell is still hyper polarised after sending an action potential, so it will take even more positive ions that usual to reach the threshold potential

Question 19

Axon hillock

Answer 19

Decision point where the it is decided whether the action potential is propagated or not propagated

Question 20

Action potential propagation in unmyelinated axons

Answer 20

1 - As an action potential develops at the initial segment, the membrane potential at this site depolarises to +30mV

2- As the sodium ions entering spread away from the open the voltage gated channels, a graded depolarisation (spread of electrical activity which causes the next part of the membrane to depolarise a bit to threshold which means an action potential will be initiated in this part of the membrane) quickly brings the membrane in segment 2 to threshold

3- An action potential develops in segment 2 (so goes up to +30mV). The initial segment begins repolarisation and is now in the refractory period.

4- As the sodium ions entering at segment 2 spread laterally, a graded depolarisation quickly brings the membrane in segment 3 to threshold. The action potential can only move forward, not backward, because the membrane at the initial segment is in the absolute refectory period of repolarisation

Question 21

Action potential propagation in myelinated axons

Answer 21

1- an action potential develops in the initial segment

2- A local current produces a graded depolarisation the brings the axolemma at node one to threshold

3- An action potential develops at node 1. The initial segment begins repolarisation (and is now in refractory period)

Note that between the nodes, the axon behaves as an excellent conductor - like a biological wire

4- A local current produces a graded depolarisation that brings the axolemma at node two to threshold

Note that the insulation of axons allows action potentials to skip between the nodes and move much faster

Question 22

Propagation in myelinated vs unmyelinated axons

Answer 22

Action potentials propagate in a continuous fashion in unmyelinated axons. Once an action potential is generated in the initial segment of the axon, it propagates the entire length of the axon. Recall that a threshold stimulus causes voltage-gated sodium channels to open. The influx of sodium ions generates an action potential. It also establishes a depolarising current that flows to the next segment and brings it to threshold. Voltage gated sodium channels open, regenerating the action potential in this segment of the axon. Current flows from this segment and depolarises the next segment to threshold, thus regenerating the action potential yet again. In this way, regeneration continues, in one direction, all the way down the axon terminals. The basis for unidirectional propagation is revealed when we take a closer look. By the end of the depolarisation phase of the action potential, all voltage gated sodium channels inactivate and voltage gated potassium channels open. These two events render this segment of the axon temporarily insensitive or refractory, to another depolarising stimulus. However, voltage gated sodium channels in the downstream segment are closed and receptive to a depolarising stimulus. Thus propagation occurs sequentially down the axon to the axon terminals. In myelinated axons, action potential propagation is a bit different. Here they propagate in a leaping or saltatory fashion. The myelin sheath consists of multiple layers of tightly wrapped glial cell membrane. But this sheath is not a continuous one. Exposed areas of the axon always membrane, known as nodes of Ranvier , occurs discrete intervals. Voltage gated sodium channels are abundant in the nodes, but are largely absent between nodes. So, action potentials are regenerated at each node, not in areas covered by the myelin sheath. However the myelin sheath does provide the insulation necessary for the rapid spread of depolarising current. And the sooner the nodes reach threshold, the faster the action potentials propagate along the axon. Saltatory conduction is extremely fast. In contrast, continuous conduction is fairly slow.Both continuous and saltatory conduction propagate action potentials over varying distances because action potentials regenerate along the way.

Question 23

What is the average speed that an action potential is propagated along an axon? (in mammals)

Answer 23

50-70 m/s

Question 24

Ligand gated ion channels

Answer 24

Ligand gated ion channels which open when a ligand (e.g. a neurotransmitter) binds

Question 25

Three ways to enhance the speed of an action potential

Answer 25

Size - bigger axon diameter = faster

Sheath - myelinated = faster (insulation prevents the loss of ions)

Saltatory conduction - Nodes of Ranvier (between myelin) all the action potential to ‘jump’ from node to node down the nerve = faster

Question 26

Key components of the synapse

Answer 26

Presynaptic cell made up of the axon terminal, vesicles, cytoskeleton, mitochondria and voltage gated Ca2+ channels

Synaptic cleft (gap between cells)

Post synaptic cell - neurotransmitter receptors (signal depolarisation) and often a thick synaptic membrane