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ICB - Neurobiology > Neurobiology 3 > Flashcards

Neurobiology 3 Flashcards

1
Q

Define depolarisation.

A

Is a reduction in the difference of electrical potential across the plasma membrane, where the potential becomes more positive inside the cell.

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2
Q

Define hyperpolarisation.

A

Is an increase in the difference of electrical potential across the plasma membrane, where the potential becomes more negative inside the cell.

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3
Q

What type of signal is depolarisation normally?

A

Usually an excitatory signal

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4
Q

What type of signal is hyperpolarisation normally?

A

Usually an inhibitory signal.

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5
Q

Which protein uses depolarisation as a inhibitory signal?

A

Rhodopsin

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6
Q

What effect does changes in electrical energy have on proteins?

A

They can change their shapes resulting in binding/release of something or open/close of channels.

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7
Q

Define the space constant (lambda).

A

The length at which the signal, V, decays to 37% of its original value, V0

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8
Q

What is the typical value of lambda for most neurons?

A

0.1-2mm

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9
Q

How do C. elegans transmit information through their neurons?

A

Voltage can spread along the axon without the need for action potentials and voltage gated sodium channels.

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10
Q

Why do C. elegans not require action potentials or sodium channels?

A

Because they have very small neurons (

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11
Q

What two things do larger organisms have to overcome the space constant?

A 
Myelination (less leakage). 
Action potentials (millisecond timescale responses).
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12
Q

Why is the same signal produced when measuring an action potential at any point down an axon?

A

Action potential generation is a self-generating mechanism. A voltage change alters the permeability of the membrane. The voltage and permeability change is spread along an axon at high speed.

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13
Q

What can action potential generation be described as?

A

An all or nothing response.

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14
Q

What is the frequency of action potentials directly related to?

A

Intensity of the stimulus.

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15
Q

What has to happen for the action potential to occur?

A

A certain threshold must be reached for the impulse to be fired.

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16
Q

What is the absolute refractory period?

A

Once an action potential has been generated, there is a period where there can be no further excitation.

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17
Q

What does the refractory period allow for?

A

This allows recovery of the ion channels.

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18
Q

Frequency modulation is used in many brain circuits, what is this?

A

Encoding information in the frequency of the action potentials.

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19
Q

What did Edgar Adrian discover?

A

Showed that the amount of depolarisation was always the same size, despite increasing the stimulus intensity. The only thing effected was the frequency of the impulse.

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20
Q

What happens when you inject an amount of current above the threshold?

A

This does not effect the action potential generated - above the threshold the same magnitude of action potential is always produced.

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21
Q

Who were the first people to measure an action potential from inside an axon?

A

Hodgkin and Huxley (1939)

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22
Q

What animal’s axon did Hodgkin and Huxley use to measure the action potential and what size was the axon?

A

Giant squid.

The axon ~1mm.

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23
Q

What method did Hodgkin and Huxley use to measure the action potential?

A

The current clamp technique.

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24
Q

Describe how Hodgkin and Huxley used the current clamp technique.

A

They measured how voltage changed over time by inserting an electrode into the cytoplasm of the giant axon.

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25
Q

Why can the current clamp technique only be used on large cells?

A

Because sharp micro-electrodes would be needed to measure the current on cell membrane region - this is too difficult with small cells.

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26
Q

What did measuring on the inside on the axon give?

A

It gave better resolution and allowed Hodgkin and Huxely predict the kinetics going on.

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27
Q

What kinetics did Hodgkin and Huxley predict using a mathematical model?

A

Predicted that there must be Na+ channels opening, followed by K+ channels and predicted precise kinetics (i.e. 3Na out and 2K in)

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28
Q

What timescale does an action potential occur on?

A

Millisecond

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29
Q

What is the resting potential primarily set by?

A

potassium ions

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30
Q

What happens when the membrane is depolarised?

A

Rapid increase in Na+ permeability, Na+ moves down its electrochemical gradient. Reaches the sodium equilibrium potential.

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31
Q

Describe the positive feedback mechanism in depolarisation.

A

The more depolarisation there is, the more Na+ channels open until equilibrium is reached.

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32
Q

Describe repolarisation.

A

Na+ channels close and K+ channels open – as the membrane gets more depolarised, the K+ channel changes shape, to allow potassium to move out of the cell, down its electrochemical gradient. The membrane potential is rapidly returned to potassium equilibrium.

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33
Q

Describe hyperpolarisation.

A

Overshoots the K+ equilibrium potential and then returns to the resting state.

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34
Q

How long does the refractory period persist?

A

Until all the voltage-gated sodium channels have recovered from inactivation.

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35
Q

What re-establishes the ionic gradients?

A

Na+/K+ ATPase activity.

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36
Q

What happens in terms of g to Na+ during an action potential?

A

The conductance of Na increases quickly, but inactivation during the refractory period then reduces conductance of Na to 0.

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37
Q

What happens in terms of g to K+ during an action potential?

A

The conductance of K+ slowly increases and only begins to decrease after hyperpolarisation.

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38
Q

Define activation.

A

Opening following depolarisation

39
Q

Define inactivation.

A

Closing independent of voltage

40
Q

Define deactivation.

A

Closing following hyperpolarisation

41
Q

Describe the kinetics of K+ channel.

A

K potassium currents activate following depolarisation but show little inactivation.

42
Q

Describe the kinetics of Na+ channel.

A

Na currents are governed by two kinetic processes activation and inactivation following depolarisation.

43
Q

What happens to both channels when the membrane potential is hyperpolarised?

A

Both Na and K channels deactivate.

44
Q

Which channel is the only channel insensitive to voltage changes?

A

Leak current channels - a K+ channel that is always open.

45
Q

What happens to the voltage sensitive channels when there is a change in voltage?

A

They change their shape in a voltage dependent manner.

46
Q

How much does the Na+ concentration change by to depolarise the membrane? And what does this mean?

A

10^-5%

This means very few ions are needed to change the membrane potential of a cell

47
Q

What does the fact very few ions are required to depolarise the membrane mean for poisoning?

A

It means the Na+/K+ ATPase pumps can be poisoned with foxglove (digitalis), and action potentials can still persist. These pumps are not essential for neurone recovery.

48
Q

What is myelin formed by?

A

Glial cells.

49
Q

What are glial cells?

A

Glial cells support non excitable cells embryonically related to neurons.

50
Q

How many glial cells are there per neuron in the mammalian brain?

A

10 glial cells per neuron

51
Q

Describe the properties of the myelin sheath and how these effect the space constant.

A

The myelin sheath (lipid) has high resistance and low capacitance - this increases the space constant.

52
Q

Where does myelination occur?

A

Myelination occurs in segments of myelinated internodes.

53
Q

What are the gaps between the internodes called?

A

These naked regions of axon are called Nodes of Ranvier.

54
Q

What do the Nodes of Ranvier mean for the propagation of the action potential?

A

The action potential velocity is increased by jumping between Nodes of Ranvier.

55
Q

What are glial cells called in the CNS?

A

Oligodendrocytes, which wrap around the axon

56
Q

What are glial cells called in the peripheral nervous system?

A

Schwann cells.

57
Q

What are astrocytes?

A

Astrocytes are a type of glial cell which provide metabolic support to neurons

58
Q

Do you all neurons have a myelin sheath?

A

No.

59
Q

Where are the ion channels that mediate action potential generation located?

A

The nodes of Ranvier

60
Q

Is there any space in the brain?

A

No.

61
Q

What is the speed of the action potential increased by?

A

Saltatory conduction.

62
Q

Which channels are found at the nodes of Ranvier?

A

Na+/K+ channels - these generate the depolarisation.

63
Q

Name one protein ensures Na+ channels are placed in the node of Ranvier and not underneath the myelin.

A

Caspr

64
Q

What type of protein is Caspr and where is it found?

A

It is an extracellular protein found either side of the node.

65
Q

Are Nodes of Ranvier within the space constant (2mm)?

A

Yes - this is enough to trigger the next action potential.

66
Q

Describe saltatory conduction.

A

Action potential ‘leaps’ from node to node- ‘jumping’ conduction.

67
Q

What did Erlanger and Gasser do?

A

Used a cathode ray oscilloscope to record action potentials.

68
Q

What did Erlanger and Gasser discover?

A

Identified different classes of nerve fibres according to their conduction velocity.
Speed increases proportionately with diameter.
Space constant increases with diameter, so charge constant spreads proportionately more.
Different conduction velocities for different nerve fibres- depends on myelination.

69
Q

How much of the human genome codes for ion channel proteins?

A

~10%

70
Q

How many genes are their for voltage gated ion channels and why are there multiple genes?

A

At least 10, as different sodium channels are used by different sub-types of neurons

71
Q

What are the 4 main things that can cause channel opening/closing?

A

Voltage changes, ligand binding, mechanical force and temperature changes

72
Q

What does mechanical force do to open ion channels?

A

Causes a stretch in sensory neurons and cause ion channels to open.

73
Q

It is thought that some channels have evolved to detect light and magnetic field, what animal is thought to use this?

A

Birds - for migration.

74
Q

Why are ion channels needed?

A

It requires a lot of energy to transport an ion across a lipid membrane – this is thermodynamically unlikely to happen

75
Q

Why must ion channels be able to open and close on very small timescales?

A

In order to allow fast action potential generation and propagation

76
Q

How were the properties of ion channels proved?

A

Using cloning of channel proteins, sequencing

77
Q

Briefly describe the patch clamping technique.

A

A glass pipette is placed over a small patch in the membrane containing the channel protein, suction allows a very tight interaction to form. This means any ions that flow through the channel protein will flow into the pipette and be recorded by electronic amplifier.

78
Q

What is a whole cell reading?

A

The clamp is continuous with the cytoplasm of the cell allowing measurements of the electrical potentials and currents from the entire cell to be made.

79
Q

Describe the method used to prepare for patch clamping.

A
  1. Express a cloned channel protein in a cell line, e.g. human embryonic kidney cells or neurons
  2. Put the glass electrode onto the cell – this is cell-attached patch clamping
  3. Apply an electric current to the cell – this electrically isolates the cell
  4. Monitor how ion flow changes whilst systematically changing the voltage
    - CsCl/TEA(Cl) blocks K+ and Na+ currents
    - Calcium ions are at physiological concentration
80
Q

Give an example of a Na+ and K+ ion channel blocker/toxin.

A 
TTX – Na+ channel blocker, from Pufferfish 
Tetraethyl ammonium (TEA) – K+ channel blocker
81
Q

Why were Xenopus Oocytes chosen to clone the ion channels?

A

Because they have few endogenous channels and were large enough (~1mm in diameter) to permit the injection of DNA and RNA.

82
Q

Describe the structure of a voltage gated sodium ion channel.

A

Almost 200aas - intracellular N and C terminus.
4 domains that come together to form a tetramer.
Each domain has 5 (or 6?) TM helices.
In each domain there is a positively charged alpha helix that senses voltage change and a pore loop which is a selectivity filter.

83
Q

At what rate do Na+ ions travel through the channel?

A

10^7- close to the theoretical maximum for sodium diffusion.

84
Q

What are the 3 states of the sodium channel?

A

Open - when membrane is depolarised, ions flow down gradient.
Inactivated - channel spontaneously closes independent of voltage (membrane still depolarised).
Closed - after hyperpolarisation of membrane

85
Q

At what rate do K+ ions travel through the channel?

A

10^7/8 - close to the theoretical maximum for potassium diffusion.

86
Q

Which part of the potassium channel is the selectivity filter?

A

The P loop (re-entrance pore loop).

87
Q

What must K+ do to enter the channel?

A

Loose its hydration shell in order to fit.

88
Q

What stabilises K+ in the filter, once its shed its hydration shell?

A

The carbonyl groups of amino acids within the pore.

Amino acids - Thr-Val-Gly-Tyr-Gly

89
Q

Why can Na+ not enter the K+ channel?

A

The pore walls are too far apart to stabilise a dehydrated Na+ ion

90
Q

What is the model suggested for voltage sensitivity in channels?

A

Ball and chain model

91
Q

Describe the ball and chain model.

A

After channel opens, a long peptide with a group of amino acids move to block to pore and switch off the channel is response to voltage change.

92
Q

Where is the long peptide described in the ball and chain model found?

A

At the N terminus - remove this and the channel will not switch off.

93
Q

How many P loops does a K+ leakage channel have?

A

2

ICB - Neurobiology (8 decks)

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