M&R Session 3 and 4 Flashcards

0
Q

How is membrane potential measured?

A

Potassium chloride filled microelectrode penetrates cell membrane conducting its potential

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1
Q

What is the basis of signalling in many types of cell?

A

Electrical potential difference across the plasma membrane

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2
Q

How is resting membrane potential expressed?

A

Potential inside relative to potential of solution outside

In mV

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3
Q

What is the range of resting potential in animal cells?

A

-20 to -90 mV

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4
Q

What is the resting potential of cardiac muscle?

A

-80 mV

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5
Q

What is the resting potential of skeletal muscle?

A

-90 mV

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6
Q

What range does the resting potential of nerve cells lie within?

A

-50 to -75 mV

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7
Q

What is the approximate resting potential of smooth muscle?

A

-50 mV

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8
Q

What are ion channels?

A

Proteins with an aqueous pore which enables ions to cross cell membranes

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9
Q

Give three properties of ion channels.

A

Selectivity for 1/a few ions
Gating by conformational change
Rapid ion flow always down electrochemical gradient

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10
Q

What dominates the membrane ionic permeability for most cells at rest?

A

Open voltage-insensitive potassium channels

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11
Q

What must be equal and opposite for no net movement of ions across a cell membrane?

A

Electrical gradient

Chemical gradient

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12
Q

In a resting cell, are the anion channels open or closed?

A

Closed

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13
Q

Permeability to which ions establishes the membrane potential?

A

Potassium

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14
Q

What assumptions are made when using the Nernst equation?

A

Membrane perfectly selective for the ion
Temperature is 37 degrees Celsius
Pressure is standard

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15
Q

What is ‘z’ in the Nernst equation?

A

Valency (charge)

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16
Q

Describe the behaviour of sodium and calcium channels in the resting cell membrane.

A

Closed but not perfectly - allow enough ions in to depolarise to -70 mV

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17
Q

What makes skeletal muscle cells have a more negative resting potential?

A

Chloride channels

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18
Q

Which ion equilibrium potential are cardiac and nerve cells close to?

A

Potassium

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19
Q

What causes cells to have a higher resting potential?

A

Lower selectivity for potassium

Increased contribution from other ion channels

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20
Q

Which two equilibrium potentials are skeletal muscle cells close to?

A

Chloride

Potassium

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21
Q

What is changing membrane potential used for?

A

Action potentials in nerve and muscle cells
Triggering of muscle contraction
Postsynaptic actions of fast synoptic transmitters
Control of neurotransmitter and hormone secretion
Transduction of sensory input to electrical activity

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22
Q

Define depolarisation.

A

Decrease in size of membrane potential from normal value

Cell interior becomes less negative

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23
Q

Define hyperpolarisation.

A

Increase in size of membrane potential from normal value

Cell interior becomes more negative

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24
Q

What changes equilibrium potential?

A

Altering membrane permeability to a particular ion

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25
Q

In which direction does the membrane potential move when it’s permeability to a particular ion changes?

A

Towards the equilibrium potential for that ion

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26
Q

Opening of which ion channels causes hyperpolarisation?

A

Potassium

Chloride

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27
Q

Opening of which ion channels causes depolarisation?

A

Sodium

Calcium

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28
Q

Which equation is used to consider the relative permeability of several ions within a membrane?

A

Goldman-Hodgkins

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29
Q

Which ion permeabilities does the Goldman-Hodgkin equation take into account?

A

Potassium
Sodium
Chloride

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30
Q

How do nicotinic receptors at the NMJ affect membrane potentials?

A

Drive it towards the average equilibrium for the ions involved

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31
Q

Describe the action of nicotinic ACh receptors.

A

Have intrinsic ion channels opened by binding of 2 ACh
Channel allows sodium and potassium through but no anions
Moves membrane potential towards the intermediate b/w sodium and potassium equilibrium potentials - 0 mV

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32
Q

How can channel activity be controlled?

A

Ligand gating
Voltage gating
Mechanical gating

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33
Q

Where are ligand-gated ion channels found?

A

At synapses that respond to extracellular transmitters

Cells that respond to intracellular messengers

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34
Q

Where are voltage-gated ion channels found?

A

In cells utilising action potentials

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35
Q

Where are mechanical-gated cells found?

A

Cells in mechanoreceptors - e.g. Carotid sinus, hair cells, stretch receptors

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36
Q

How do mechanical-gated ion channels work?

A

Membrane deformation causes the channels to open or close

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37
Q

How is fast synaptic transmission carried out?

A

The receptor protein is also an ion channel which open upon transmitter binding

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38
Q

Give an example of a fast synaptic transmission receptor.

A

Nicotinic ACh

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39
Q

How do excitatory synapses work?

A

Ligand-gated channels are opened –> membrane depolarises as cations move in –> excitatory post-synaptic potential (EPSP) generated

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40
Q

What is different about and action potential and an EPSP?

A

EPSP has a longer time course

EPSP can be graded by the amount of transmitter which binds

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41
Q

Give two examples of transmitters which can be used at excitatory synapses.

A

ACh

Glutamate

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42
Q

How do inhibitory synapses work?

A

Open ligand-gated channels –> hyperpolarisation –> inhibitory post synaptic potential (IPSP) generated

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43
Q

How does an IPSP compare to an AP?

A

IPSP has a longer time course than an AP

IPSP uses glycine (in spinal cord) and GABA

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44
Q

How does slow synaptic transmission occur?

A

Direct G-protein gating

Gating via an intracellular messenger

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45
Q

What is a G-protein?

A

A 7-domain transmembrane receptor

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46
Q

Describe two properties of G-protein gating.

A
Localised
Quite rapid (not as fast as fast synaptic)
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47
Q

Describe the method of gating via an intracellular messenger.

A

Occurs throughout cell
Amplification by cascade produces new intracellular chemicals
G-protein receptor –> enzyme –> intracellular messenger/protein kinase –> channel

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48
Q

Why is hyperkalaemia very dangerous?

A

Cardiac myocyte membranes become easily excited –>contraction more easily stimulated

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49
Q

What is the function of Na/K-ATPase in the resting membrane potential?

A

Contributes a few mV directly by movement of one +ve charge out per cycle
May modify activity
Indirectly accountable for whole membrane potential due to it establishing ion gradients

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50
Q

What must happen for the voltage across a cell membrane to rapidly change?

A

Threshold level must be reached

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51
Q

What is the term given to the response of a cell dependent on whether the threshold level is reached?

A

All or nothing

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52
Q

How does the amplitude vary as it travels along an axon?

A

It remains constant

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53
Q

What causes the repolarisation profile of skeletal muscle to vary in comparison to that of other cells?

A

Different ion channels

T-tubules

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54
Q

Describe the action potential in a cardiac ventricle cell.

A

-90 to +30 mV

Over 100 Ms

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55
Q

Describe the action potential in a sino-atrial node cell.

A

-60 to +30 mV

Over 100 Ms

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56
Q

Describe the action potential in a skeletal muscle cell.

A

-90 to +40 mV

Over 0.5 Ms

57
Q

Describe the action potential in an axon.

A

-70 to + 30 mV

Over 0.5 Ms

58
Q

Why does opening chloride channels in an axon have minimal effect?

A

The membrane potential is -70 mV and its equilibrium potential is -96 mV

59
Q

Which is the most variable equilibrium in muscle cells?

A

Chloride

60
Q

Why is the lipid bilayer referred to as a good capacitor?

A

Can store a lot of charge

Separates two good conductors

61
Q

What is the effect of reducing extracellular sodium on the action potential?

A

It reduces the overshoot in membrane potential to the point where it no longer becomes -ve

62
Q

What changes in parallel to the change in sodium equilibrium?

A

The peak of the action potential

63
Q

What is thought to cause the upstroke in an action potential?

A

A large increase in sodium permeability

64
Q

What magnitude of movement of sodium ions is required to generate an action potential in an axon of 1 micrometer diameter?

A

> 0.4%

65
Q

What different methods can be used to investigate axon potential generation?

A

Voltage clamping
Change ionic concentrations
Patch clamping

66
Q

What is the axon hillock?

A

An area with a high density of sodium channels

67
Q

What takes place at the axon hillock?

A

Depolarisation to threshold value activates an axon potential here

68
Q

What causes the sodium conductance during an action potential to quickly fall away?

A

Sodium channel inactivation

69
Q

What causes the delay in potassium channel closure during an action potential?

A

The potassium conductance

70
Q

What happens during upstroke of the action potential?

A

Sodium channels open –> sodium influx –> depolarisation –> to threshold = entry to feedback loop

71
Q

How is the rate of sodium channel opening increased?

A

Greater membrane depolarisation

72
Q

What is the basis of the all or nothing response?

A

Whether the cell enters positive feedback

73
Q

Why does the cell not respond if the threshold value is not met?

A

Too few sodium channels are open

74
Q

What happens during the downstroke of the action potential?

A

Depolarisation causes inactivation of sodium channels and after a short delay opens potassium channels –> sodium influx stopped and potassium efflux takes place –> repolarisation

75
Q

What is the absolute refractory period?

A

No action potential generated no matter how much you stimulate it

76
Q

What is the relative refractory period?

A

Sodium channels recover from inactivation to restore membrane excitability

77
Q

Compare the duration of the absolute refractory period and the relative refractory period.

A
ARP = fixed duration - first millisecond
RRP = variable duration
78
Q

What causes a shorter RRP?

A

More hyperpolarisation (–> faster recovery)

79
Q

Can sodium channels open from an inactivated state?

A

No

80
Q

How are sodium channels recovered from inactivation?

A

They must be hyperpolarised to become closed and then depolarise to be opened

81
Q

Can sodium channels be inactivated before the threshold potential is reached?

A

Yes

82
Q

What is accommodation in relation to cell membranes?

A

How the membrane potential determines how excitable the membrane is

83
Q

What is the affect on a cell membrane of a longer stimulus?

A

Increased time taken to reach membrane potential
More inactivated sodium channels
Lowered action potential peak

84
Q

What happens to the threshold potential as the time taken to reach it increases?

A

It becomes more positive

85
Q

Does the action potential reach the threshold if it’s peak is lowered by a long stimulus?

A

No

86
Q

Will a membrane which is accommodated fire an action potential if the original threshold is surpassed?

A

No

87
Q

Where are the ~10,000 continually firing synapses in an axon integrated?

A

At the dendritic tree

88
Q

What is the basic structure of a sodium channel?

A

Repeats I-IV of 6 membrane spanning domains

Functional channel = 1 alpha-subunit

89
Q

What is the voltage sensor of a sodium channel?

A

S4 region with lots of +ve residues

90
Q

Where is the pore region in a sodium channel?

A

Domains 5-6

91
Q

What happens to a sodium channel when it becomes inactivated?

A

Inactivation particle binds 6-1 –> conformational change –> pore blocked

92
Q

What happens to an inactivated sodium channel to recover it?

A

Membrane polarised –> change in voltage force –> conformational change –> inactivation particle released

93
Q

Describe the structure of a potassium channel.

A

Single 6 membrane-spanning domains unit
Functional channel = 4 alpha-subunits
Similar to sodium channel, just a quarter of the size

94
Q

What prevents passage of sodium ions through potassium channels?

A

Its amino acid sequence means the smaller ions cannot pass through easily

95
Q

What is the action of local anaesthetics?

A

Block sodium channels

96
Q

Which two pathways can local anaesthetics take?

A

Hydrophobic (no use-dependent)

Hydrophilic (use-dependent)

97
Q

What determines which pathway a local anaesthetic takes?

A

It’s lipid solubility

98
Q

Describe the mechanism of the hydrophobic pathway.

A

Pass through lipid membrane –> block sodium channel pore –> as more action potentials fire more channels are opened –> more channels are blocked –> pain becomes duller

99
Q

In which activation state of sodium channels do lipid soluble local anaesthetics have greatest affinity for?

A

Inactivated

100
Q

When is binding of local anaesthetics in the hydrophobic pathway easiest?

A

When sodium channels are open

101
Q

Describe the mechanism of the hydrophilic pathway.

A

Local anaesthetic becomes charged by combination w/ proton –> binds to and blocks open sodium channel

102
Q

What must happen for a use-dependent local anaesthetic to work?

A

The sodium channels must be opened initially

103
Q

In what order do local anaesthetics block axons?

A

Small myelinated
Un-myelinated
Large myelinated

104
Q

Is initial pain experienced in the use of local anaesthetics?

A

Yes, sodium channels are opened so some initial action potentials are fired

105
Q

Give two examples of disease states which affect conduction of action potentials in the CNS.

A

Multiple sclerosis

Devic’s disease

106
Q

Give two examples of diseases which affect conduction of action potentials in the PNS.

A

Landry-Guillan-Barre syndrome

Charcot-Marie-Tooth disease

107
Q

Which nerves does Devic’s disease affect?

A

Optic

Spinal cord

108
Q

What are the four classes of peripheral axons?

A

A-alpha
A-delta
B
C

109
Q

What are A-alpha peripheral axons?

A

Sensory fibres from muscle spindles

Motor neurones to skeletal muscle

110
Q

What are A-delta peripheral axons?

A

Sensory fibres from pain and temperature receptors

111
Q

What type of pain do A-delta peripheral axons give rise to?

A

Sharp, localised pain

112
Q

What are B peripheral axons?

A

Preganglionic neurones of the ANS

113
Q

What are C peripheral axons?

A

Sensory fibres from pain, temperature and itch receptors

114
Q

What kind of pain do C peripheral axons give rise to?

A

Diffuse pain

115
Q

What is diphasic recording?

A

Stimulating and recoding electrodes are placed on the axon during extracellular recording of an action potential

116
Q

What is monophonic recording?

A

A portion of axon is deliberately damaged underneath/before the recording electrode to stop the action potential

117
Q

What is a nerve fibre made up of?

A

Several axons w/ different diameters

118
Q

How is the action potential of a nerve fibre described?

A

Compound

119
Q

What does increasing the distance from the stimulus that the action potential is measured do?

A

Gives greater action potential peak separation (monophasic recording)

120
Q

What is the length constant (lambda)?

A

The distance taken for the action potential to fall by 37% (1/e) of its original value

121
Q

What does the length constant depend on?

A

How far along the axon the action potential travels

122
Q

Describe the mechanism of the local current theory

A

Sodium in –> repels +ve ions w/in axon –> ions spread in either direction –> immediate local current

123
Q

Does the immediate local current depolarise as much as the original stimulus?

A

Nope

124
Q

What affect does an increase in capacitance have on a axon’s electrical properties?

A

Increases time taken to reach a steady voltage

Does not directly affect length constant

125
Q

What decreases length constant at the action potential downstroke?

A

Open potassium channels

126
Q

What prevents right to left transmission of nerve impulses?

A

Inactivation of sodium channels

127
Q

At what diameters is it not worth having myelination?

A

< 1 micrometer

128
Q

What holds the myelin sheath tightly in place around axons?

A

Proteins

129
Q

Describe the function of Schwann cells in myelination.

A

Myelinate PNS axons

Myelinate one axon each by pushing previous layers further from the centre

130
Q

Describe the role of oligodendrocytes in myelination.

A

Myelinate CNS axons

Myelinate up to 50 axons each

131
Q

How does myelination increase the speed of action potential transmission?

A

Saltatory conduction

132
Q

How does myelination affect the electrical properties of an axon?

A

~100x increase in membrane resistance
~100x decrease in membrane capacitance
Therefore…
Increase length constant and decrease time constant

133
Q

What is found at a Node of Ranvier?

A

Increased densities of ion channels

134
Q

How does saltatory conduction work?

A

Local circuit current depolarises the next node of Ranvier above threshold –> initiates an action potential

135
Q

What is the relationship b/w conduction velocity and diameter of axon in unmyelinated axons?

A

Velocity is proportional to the square root of diameter

136
Q

How is local current spread altered in saltatory conduction?

A

It is greatly increased

137
Q

How does demyelination alter the electrical properties of an axon membrane?

A

Decreases its resistance and increases its capacitance

138
Q

What is the result of demyelination of an axon?

A

The action potential at the subsequent node is not above threshold –> no conducted

139
Q

Briefly describe the process of Multiple Sclerosis.

A

Multiple areas of CNS damage –> areas determine symptoms –> eventually leads to axon damage

140
Q

What magnitude is the ion movement during the generation of an action potential?

A

Small - relatively few ions move

141
Q

Is Na/K-ATPase used for action potential repolarisation?

A

No