Lecture 2 - Chapter 2/4: Action Potentials are Generated by Ion Currents Flashcards

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1
Q

What is electric current?

A

Flow of electrical charge, i.e. flow of potassium and sodium (ampere = coulomb/second)

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2
Q

What is membrane resistance?

A

A measure of how much the membrane opposes the passage of electrical charge (through ion channels)

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3
Q

What is membrane conductance?

A

The permeability of the cell membrane to those ions

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4
Q

What is voltage?

A

Difference in charge between two points (i.e. membrane gradient). It creates energy that pushes charge to move.

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5
Q

What is the membrane potential?

A

The voltage difference between the inner and outer surface of the cell membrane.

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6
Q

What is meant by the fact that membranes are capacitors?

A

The membrane, composed of a lipid bilayer, is impermeable to ions. It can therefore store charges.

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7
Q

What technique is able to control the membrane potential and simultaneously measure their underlying permeability changes? And what animal was used to study electrical signals?

A

A voltage clamp, first used in squids. Squids have enormous axons of 1 mm in diameter compared to 1-2 um in mammals.

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8
Q

How is voltage clamp measurement achieved?

A

The device is able to control membrane potentials at any level desired.

  1. Here, the membrane potential is measured by an electrode placed inside the cell, e.g. on an axon. This electrode is connected to the voltage clamp amplifier.
  2. The amplifier compares this membrane potential with the desired (command) potential.
  3. When Vm/membrane potential is different from the command potential, the clamp amplifier injects current into the axon through a second electrode. This way the membrane potential becomes the same as the command potential.
  4. The current flowing back into the axon, and thus across its membrane, can be measured here.
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9
Q

What is a capacitive current?

A

The capacitive current determines how fast the cell membrane potential responds to the flow of ion channel currents. It is the flow in membrane current due to a changing potential of the electrode which charges or discharges the membrane (i.e. the capacitor) → thus only flows when the membrane potential is changing.

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10
Q

What happens when the membrane potential is hyperpolarized from the resting level (-65 mV) to -130 mV?

A

There’s redistribution of charge across the axonal membrane. The capacitive current is a nearly instanteneous. Besides this, very little current flows when the membrane is hyperpolarized.

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11
Q

What happens when the membrane potential is depolarized from -65 mV to 0 mV?

A

First, there is a outward capacitive current. After this, a transient inward current is rapidly produced, where positive charges enters the cell. This results in a more slowly rising delayed outward current.

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12
Q

What ions are (probably) responisble for the transient inward and delayed outward current?

A
  • Transient inward current → sodium
  • Delayed outward current → potassium
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13
Q

Name three ways how it can be tested what ions are involved e.g. depolarization or hyperpolarization.

A
  1. By determining at what membrane potential the current reverses and comparing it to the electrochemical equilibrium potential of ions in solution
  2. By changing the external concentrations of certain ions and testing if the current is altered or reversed.
  3. By blocking certain channels and testing if this also block the current.
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14
Q

So it’s most likely sodium is responsible for the transient inward current during depolarization. Already mentioned is that this can be tested by blocking sodium channels. How is this achieved?

A

By blocking the voltage-gated Na+ channels with tetrodotoxine (TTX) (but this wasn’t possible in the earlier days so they used something else)

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15
Q

So it’s most likely sodium is responsible for the transient inward current during depolarization. Already mentioned is that this can be tested by changing the external/extracellular concentration of sodium ions. What happens to the inward current when sodium is removed from the extracellular space?

A

The inward current changes to an outward current. When sodium is recovered extracellularly, the inward current is also recovered. This shows that for this inward current, extracellular sodium is needed.

(This can also be tested for potassium, where potassium is removed intracellularly, which removes the delayed outward current).

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16
Q

Another method that is commonly used to research membrane potentials is the Patch Clamp method. What’s different in this method compared to the Voltage Clamp method?

A
  • The Voltage Clamp method used giant squid axons to control the membrane potential and simultaneously measure their underlying permeability changes.
  • The Patch Clamp method is used to study the function of single ion channels in cells.
17
Q

Explain how the Patch Clamp method works.

A
  1. Patch-clamping setup → a micropipette (diameter 1 µm) is placed against a cell.
  2. Membrane patch isolation → gentle suction is applied to form a tight seal between the pipette and the plasma membrane. Typically only one or few channels will be in the membrane within the pipette.
  3. The flow of ions is recorded while the membrane is subjected to a depolarizing step in voltage, yielding traces of individual Na+ currents during channel opening.
18
Q

What can be recorded when multiple ion channels are sealed between the pipette and the plasma membrane?

A

The macroscopic sodium flow

19
Q

Where is the ionic current/flow proportionate to?

A

Ionic current = conductance x (membrane potential - equilibrium potential)

Note: conductance is permeability

20
Q

How does ion conductivity increase?

A

By the opening/closing of channels.

So what you see in this picture, is that first the ion conductance of sodium increases rapidly (which means that sodium channels are opening), which is followed by a slight increase in potassium conductance (i.e. opening of potassium channels).

21
Q

What happens during a resting membrane potential?

A

During the resting membrane potential, there’s a higher potassium conductance than for sodium (gK > gNa). Furthermore, there’s more Na+ outside the cell then inside and there’s more K+ inside the cell then outside.

22
Q

Explain the steps that occur during an action potential.

A
  1. Na+ channels open → gNa increases
  2. Na+ enters the cell
  3. Membrane potential gets depolarized further
  4. Electrochemical driving force for Na+ diminishes (when the membrane potential becomes more positive, more Na+ channels close again)
  5. K+ channels open and gK increases and the Na+ current is inactivated
  6. K+ exits the cell (and the membrane potential gets less positive → repolarization)
  7. K+ channels also close

Note: as the picture also states → any depolarizing force will bring the membrane potential closer to threshold. This will cause Na+ channels to open.

23
Q

What is meant by the fact that action potentials are self-supported and are thus termed as a ‘all- or nothing event’ and why is this important?

A

That an action potential is always a full response. Either a stimuli stimulates the membrane to reach the threshold or the stimuli isn’t strong enough to stimulate the membrane to reach the threshold. So, there’s no such thing as a strong or weak action potential.

This minimizes the possibility that information will be lost along the way.

24
Q

What’s the refractory period?

A

The last step of an action potential is the closing of the potassium channels. But since these channels are a little slow with closing, K+ ions are still capable to exit the cell. This makes the membrane potential go even more negative than the resting membrane potential, which is called hyperpolarization. During this event, the cell is not capable of creating a new action potential. This is called the refratory period.

25
Q

How does the cell recover during the refractory period (i.e. how does the cell go back to its resting membrane potential)?

A

There’s a sodium potassium pump, which is responsible for putting sodium and potassium back in place. So it ensures that more sodium is moved out of the cell than K+ exits the cell via its K+ channel. This restores the membrane potential to its resting membrane potential.

26
Q

What is meant by the fact that action potentials can self propagate?

A

It means that one action potential automatically triggers the neighboring membrane areas into producing an action potential via local currents. Local currents induce depolarisation of the adjacent axonal membrane and where this reaches a threshold, further action potentials are generated.

Thus once threshold is reached action potentials always propagate down the axon to the synaptic region of the axon.

27
Q

Action potentials do not propagate backwards. What is meant by this and how is this possible?

A

An action potential is propagated when the local current that is induced by the first action potential triggers the adjacent (Na+) channels to initiate the next action potential, so that the action potential can be moved down the axon to the synaptic region of the axon.

Action potentials can not propagate backwards means that action potentials can not be activated at the same place where the previous action potential has occured. This is due to the fact that the sodium channels that have been opened by the previous action potential are still inactivated. Therefore, at this place an action potential can not propagate.

28
Q

What process speeds up action potential propagation?

A

Myelination → myelin is produced by glial cells and causes the action potential to propagate uicker since myelin is a very good isolator. This allows neurotransmission to be very fast.

29
Q

Just study this picture. If you understand this picture, you also probably understand everything that is discussed before.

A

Ok