Action Potential Flashcards

1
Q

What is the action potential?

A
  • Change in voltage across membrane
  • Depends on ionic gradients and relative permeability of the membrane
  • Only occurs if a threshold level is reached
  • All or nothing
  • Propagated without loss of amplitude
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2
Q

What initiates an action potential and where is it initiated?

A

Depolarisation to threshold initiates an action potential at the axon hillock

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3
Q

What happens if the conductance to an ion is increased?

A

If the conductance (g) to any ion is increased the membrane potential (Vm) will move closer to the equilibrium potential for that ion.

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4
Q

How is conductance increased?

A

Opening more ion channels - The conductance of the membrane to a particular ion is dependent on the number of channels for the ion that are open.

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5
Q

What is the resting membrane potential?

A

Neurons have a negative concentration gradient most of the time, meaning there are more positively charged ions outside than inside the cell. This regular state of a negative concentration gradient is called resting membrane potential.

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6
Q

Are there more sodium/potassium ions inside or outside the cell during the resting potential?

A

More sodium ions outside

More potassium ions inside

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7
Q

The concentration of ions isn’t static though! Ions are flowing in and out of the neuron constantly as the ions try to equalize their concentrations. The cell however maintains a fairly consistent negative concentration gradient (between -40 to -90 millivolts). How?
Name 3 ways

A

The neuron cell membrane is super permeable to potassium ions, and so lots of potassium leaks out of the neuron through potassium leakage channels (holes in the cell wall).

The neuron cell membrane is partially permeable to sodium ions, so sodium atoms slowly leak into the neuron through sodium leakage channels.

The cell wants to maintain a negative resting membrane potential, so it has a pump that pumps potassium back into the cell and pumps sodium out of the cell at the same time.

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8
Q

Which channels are closed during the resting potential?

A

During the resting state (before an action potential occurs) all of the gated sodium and potassium channels are closed. These gated channels are different from the leakage channels, and only open once an action potential has been triggered. We say these channels are “voltage-gated” because they are open and closed depends on the voltage difference across the cell membrane.

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9
Q

What are the 3 states a voltage gated sodium channel can exist in?

A

Deactivated (closed) - at rest, channels are deactivated. The m gate is closed, and does not let sodium ions through.

Activated (open) - when a current passes through and changes the voltage difference across a membrane, the channel will activate and the m gate will open.

Inactivated (closed) - as the neuron depolarizes, the h gate swings shut and blocks sodium ions from entering the cell.

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10
Q

Describe depolarisation

A

Depolarization - makes the cell less polar (membrane potential gets smaller as ions quickly begin to equalize the concentration gradients) . Voltage-gated sodium channels at the part of the axon closest to the cell body activate, thanks to the recently depolarized cell body. This lets positively charged sodium ions flow into the negatively charged axon, and depolarize the surrounding axon. We can think of the channels opening like dominoes falling down - once one channel opens and lets positive ions in, it sets the stage for the channels down the axon to do the same thing. Though this stage is known as depolarization, the neuron actually swings past equilibrium and becomes positively charged as the action potential passes through!

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11
Q

How do we know which direction ions will move?

A

Depolarisation - Na+ electric and chemical gradients inwards - Na+ moves in moving Vm closer to ENa - generally will not reach the Na+ equilibrium potential bc other ion channels are open
As membrane potential rises above 0mV, electrical gradient changes in direction
When gradients @ equilibrium =, no net movement of Na+
K+ then has to move out to make membrane potential more -ve (the chemical conc gradient is slightly more then the electrical gradient here)

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12
Q

Describe repolarisation

A

brings the cell back to resting potential. The inactivation gates of the sodium channels close, stopping the inward rush of positive ions. At the same time, the potassium channels open. There is much more potassium inside the cell than out, so when these channels open, more potassium exits than comes in. This means the cell loses positively charged ions, and returns back toward its resting state.

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13
Q

Describe hyperpolarisation

A

makes the cell more negative than its typical resting membrane potential. As the action potential passes through, potassium channels stay open a little bit longer, and continue to let positive ions exit the neuron. This means that the cell temporarily hyperpolarizes, or gets even more negative than its resting state. As the potassium channels close, the sodium-potassium pump works to reestablish the resting state.

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14
Q

What is the all or nothing principle?

A

Action potentials work on an all-or-none basis. This means that an action potential is either triggered, or it isn’t – like flipping a switch. A neuron will always send the same size action potential

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15
Q

What determines the strength of a signal?

A

When the brain gets really excited, it fires off a lot of signals. How quickly these signals fire tells us how strong the original stimulus is - the stronger the signal, the higher the frequency of action potentials. There is a maximum frequency at which a single neuron can send action potentials, and this is determined by its refractory periods.

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16
Q

What is absolute refractory period?

A

Absolute refractory period: during this time it is absolutely impossible to send another action potential. Nearly all sodium channels inactivated, and make it so no sodium will pass through. No sodium means no depolarization, which means no action potential. Absolute refractory periods help direct the action potential down the axon, because only channels further downstream can open and let in depolarizing ions.

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17
Q

What is relative refractory period?

A

Relative refractory period: during this time, it is really hard to send an action potential. Sodium channels recovering from inactivation.This is the period after the absolute refractory period, when the h gates are open again. However, the cell is still hyperpolarized after sending an action potential. It would take even more positive ions than usual to reach the appropriate depolarization potential than usual. This means that the initial triggering event would have to be bigger than normal in order to send more action potentials along. Relative refractory periods can help us figure how intense a stimulus is - cells in your retina will send signals faster in bright light than in dim light, because the trigger is stronger.

18
Q

What is a purpose of refractory periods?

A

Refractory periods also give the neuron some time to replenish the packets of neurotransmitter found at the axon terminal, so that it can keep passing the message along. While it is still possible to completely exhaust the neuron’s supply of neurotransmitter by continuous firing, the refractory periods help the cell last a little longer.

19
Q

How can we show experimentally that Na+ is responsible for AP depolarisation?

A

• The straight line is the predicted change in ENa as external [Na+] is
reduced.
• The peak of the action potential changes in a manner parallel to the changes in ENa.
• This supports the idea that the upstroke of the action potential is due to a large increase in permeability to Na+ ions.

As Na+ decrease on outside
Peak becomes more -ve
Slopes parallel to sodium equilibrium potential
Changing sodium on outside, changing value of quilibrium potential
Sodium influx key to generating action potential

20
Q

How much does each AP increase the sodium in the axon?

A

So each action potential increases [Na+] in the axon by only 40µM. If the resting [Na+] is 10mM this represents an increase of 0.4%. For a larger diameter axon the change in concentration will be even smaller.

21
Q

What does a voltage clamp do?

A

Enables membrane currents to be measured at a set potential
At 0mv, K+ moves out of cell
Open more slowly than Na+ channels
Do not inactivate
When return memb potential back to -70, k+ channels take a while to close
-70 all Na+ closed
At 0mv, influx of sodium
Maintain depolarisation but current decreases to 0
Na+ channels undergo inactivation
Inactivate quickly after opening

22
Q

Describe how the time course of conductance changes during an action potential

A

Conductance - no of channels open
At rest closed, memb potential negative enough so they are closed
When open, up stroke, then number of open sodium channels decreased due to inactivation
Number of k+ channels increases after a delay as membrane potential comes back K+ channels close slowly
Membrane potential comes back down to a velue a bit more negative than resting potential
Vg k+ channels stay open or a while - drives memb potential towards -ve as vg+channels close, memb potential go back to resting

23
Q

Describe the channel activity during an axonal AP

A
Raise to threshold, 
Vg Na+ channels open
Na+ influx
Depolarisation - initiates more Na+ channels to open
Positive feedback needed to generate AP
All or nothing
Need to open enough 
Not an ap for every depolarisation 
Vg k+ open
K+ efflux
Na+ inactivate
Ap back down
Not many ions have to move
Na+/k+ pump is not involved in repolarisation 
Role of pump maintains gradient in background
24
Q

Describe recovery after an action potential

A

Cant open more channels after ap as Na+ channels inactivated so no 2 aps after each other
In rrp sodium channels recovering from inactivation
When closed they can open
From open state they then become inactivated
Part of channel plugs the pore to inactivate
They need to recover before passing current
When memb hyperpolarises sodium channels recover back to closed state

25
What is the basic structure of a voltage gated Na+ channel?
6tm a helicies 4th has +ve charges In depolarisation, eperience a force When memb pot changes, conformational change Then inactivation particle can enter pore Functional Na+ channel is only one alpha subunit
26
What is the basic structure of a voltage gated K+ channel?
Subuuit 1/4 of the size of a Na+ channel 1 alpha subunit does not make a functional channel - need 4 One α subunit is ¼ of a channel. A functional K+ channel comprises four individual α subunits
27
How do local anaesthetics work? Give an example
E.g. procaine Local anaesthetic block sodium channels through membrane More likely to block channel a when channel open Uncharged to get through but charged to have an effect 2 pathways 1) hydrophobic - charges outside the pore - goes through membrane 2) hydrophilic (use dependence)- charges in the pore
28
What does the relative importance of the hydrophobic and hydrophilic pathways vary according to?
The lipid solubility of the drug
29
In which order do local anaesthetics block axons in?
1. small myelinated axons 2. un-myelinated axons 3. large myelinated axons
30
How does conduction velocity vary with axon diameter
Increases as dia increases
31
Name classes of peripheral axons and give examples
``` A alpha A beta A gamma A delta B C ``` Aα – sensory fibres from muscle spindles, motor neurones to skeletal muscle Aδ – sensory fibres from pain and temperature receptors (sharp localized pain) B – preganglionic neurones of autonomic nervous system C – sensory fibres from pain, temperature and itch receptors (diffuse pain)
32
Explain how to reassure compound action potentials and conduction velocity
A nerve fibre comprises several axons with different diameters Damage one section Measure how long action potential takes to reach certain point Extracellular potential between points a and b Measuring changes in extracellular membrane potential Several peaks - indicates population of axons in the nerve fibre that will conduct an ap at different velocities Time it takes between stimulation and AP arriving at respective recording electrodes will be different as increase in gaps between them Axons - different conduction velocities
33
Explain local current theory
Injection of current into an axon will cause the resulting charge to spread along the axon and cause an immediate local change in the membrane potential.
34
What are resistance and capacitance? How do they affect spread of local current?
Capacitance, C, is the ability to store charge. This is a property of the lipid bilayer. The membrane resistance depends on the number of ion channels open. The lower the resistance the more ion channels are open. High capacitance – voltage changes more slowly in response to current injection High resistance – change in voltage spreads further along the axon
35
Explain the propagation of the action potential
Raise to threshold - initiate ap Ap moves along axon Inactivation stops it going back Increase diameter - faster conduction
36
What is the myelin sheath?
Schwann in pns - wrap around axon many times Oligodedrocytes in CNS Lots of ion channels at nodes, not many between nodes
37
Explain saltatory conduction
The myelin sheath acts as a good insulator thereby causing the local circuit currents to depolarize the next node above threshold and initiate an action potential. Local depolarisation spreads to next node The action potential “jumps” from node to node allowing a much faster conduction velocity. An action potential occurs only at the nodes.
38
How does myelination affect conduction?
Myelin sheath improves conduction by: • large increase in membrane resistance (Rm) • large decrease in membrane capacitance (Cm) • these increase length constant (λ) • slight decrease in time constant (τm) Conduction Velocity ∝ λ / τm
39
What are some diseased affecting conduction of the action potential?
``` Central Nervous System • Multiple sclerosis – all CNS nerves • Devic’s disease – optic and spinal cord nerves only Peripheral Nervous System • Landry-Guillain-Barre syndrome • Charcot-Marie-Tooth disease ``` These diseases result from breakdown or damage the myelin sheath. Multiple sclerosis is the most common demyelinating disease.
40
How is the AP affected in areas of demyelination?
In regions of demyelinaion the density of the action current is reduced because of resistive and capacitive shunting.