Lecture 4 - Electrical Signals of Nerve Cells (The Action Potential)

Question 1

How do you calculate an ion’s conductance?

Answer 1

An ion’s conductance is equal to the current it carries divided by its driving force.

g_ion = I_ion / (V_m - E_ion)

Question 2

True or False?:

According to Hodgkin & Katz: At rest, P_K : P_Na : P_Cl = 1 : 0.04 : 0.45. At the peak of the action potential, P_K : P_Na : P_Cl = 1 : 0.04 : 20.00.

Answer 2

False

At rest, P_K : P_Na : P_Cl = 1 : 0.04 : 0.45. At the peak of the action potential, P_K : P_Na : P_Cl = 1 : 20.00 : 0.45.

Question 3

True or False?:

Excitable tissue can both sense and produce electricity.

Answer 3

True

Question 4

Explain the states of K⁺ channels during an action potential.

Answer 4

K⁺ channels are binary and only exist in the open or closed states. They are closed when the membrane potential is negative and opened when the membrane potential is positive. Though, they have a slight delay. They open shortly after the membrane potential becomes positive, allowing K⁺ ions to flow out of the cell in order to reestablish a negative membrane potential.

Question 5

True or False?:

All voltage-gated Na⁺ channels are open at hyperpolarized potentials.

Answer 5

Fewer than 100% of voltage-gated Na⁺ channels are open at hyperpolarized potentials.

Question 6

Who did grotesque experiments with the hind quarters of a frog on zinc bases with copper wires to complete a circuit where the frog legs twitched that led to the proposal that animal tissues generate electricity by using a “vital energy”? Who proposed that the tissue is simply responding to an electic current generated by the redox reaction between the copper and zinc used? Who was right?

Answer 6

Luigi Galvani

Alessandro Volta

Galvani was right! Much of the energy produced was electrical energy generated by the tissue. (Though, Volta was right and he did indeed create a battery.)

Question 7

True or False?:

If you stimulate a neuron, you don’t just get the response to your stimulation. Rather, you can acrtually measure an induced current from the neuron itself.

Answer 7

True

Question 8

Who developed the voltage clamp method?

Answer 8

Kenneth Cole

Question 9

True or False?:

Potassium will always want to flow out of the cell as long as you are above -84 mV.

Answer 9

True

Question 10

True or False?:

Hodgkins & Huxley used voltage clamp measurements to calculate the individual membrane conductances for Na⁺ and K⁺ during the action potential.

Answer 10

True

Question 11

What is conductance (g)?

Answer 11

Conductance is a measure of how easily current flows across the membrane. It is the inverse of resistance.

Question 12

What happens to the transient inward current as you increase the hyperpolarization voltage steps in a voltage clamp recording? Why?

Answer 12

The transient inward current gets bigger, then smaller, and eventually reverses direction (becomes outward) at +65 mV. This happens because as the voltage increases, the driving force for sodium gets lower until the membrane potential passes E_Na. After that point, the driving force increases but in the opposit direction, which is why the transient inward current becomes an outward current.

Question 13

True or False?:

Depolarizing the cell beyond the normal resting potential usually does not cause any additional channels to open.

Answer 13

False

Hyperpolarizing the cell beyond the normal resting potential usually does not cause any additional channels to open.

Question 14

What experiment did Matteucci conduct? What did it prove?

Answer 14

Matteucci took Galvani’s model but modified it. He crushed the end of a muscle, attached a second muscle’s nerve to it, and then stimulated the first muscle with a copper and zinc battery. He observed that the first muscle would contract along with the second through a signal sent through the crushed muscle and along the nerve. This proves that the muscle isn’t just responding to electricity, but is generating it as well.

Question 15

What happens to the delayed outward current as you increase the hyperpolarization voltage steps in a voltage clamp recording?

Answer 15

The delayed outward current gets progressively bigger.

Question 16

True or False?:

TTX (tetrodotoxin) block voltage-gated K⁺ channels and TEA (tetraethyl-ammonium) blocks voltage-gated Na⁺ channels.

Answer 16

False

TTX (tetrodotoxin) block voltage-gated Na⁺ channels and TEA (tetraethyl-ammonium) blocks voltage-gated K⁺ channels.

Question 17

If you increase the extracellular potassium concentration, what happens to the action potential?

Answer 17

The undershoot of the action potential goes lower.

Question 18

What is the difference between the absoute refractory period and the relative refractory period?

Answer 18

During the absolute refractory period, the Na⁺ channels are inactivated and it is imposssible to fire another action potential. During the relative refractory period, some (but not all) Na⁺ channels are reactivated so you can get an action potential, but not a full one.

Question 19

True or False?:

Depolarizing the cell from the normal resting potential activates voltage-sensitive ion channels, resulting in measurable currents.

Answer 19

True

Question 20

What is the voltage clamp technique?

Answer 20

Voltage clamp is a technique to hold or “clamp” a cell’s membrane potential at a fixed value. Since the voltage is clamped, you can just measure the currents that flow and since voltage is fixed, current is inversly proportional to resistance. If you can fix voltage, measuring current will give you the resistance, which represents channels opening and closing.

While performing the technique, when the actual V_m differs from the command voltage, the electrode injects current to move the V_m to where it should be.

Question 21

If you systematically decrease the extracellular concentration of sodium, what happens to the action potential?

Answer 21

The peak of the action potential gets lower and the whole action potential gets longer in duration.

Question 22

What happens if you treat neurons with pronase?

Answer 22

Intracellular pronase removes the ability for Na⁺ channels to inactivate. It essentially removes the “ball” from the “ball and chain” model. Like a K⁺ channel, once activated, the pronase treated Na⁺ channel stays open for as long as the cell is depolarized.

Question 23

Why is there a refractory period during which a membrane cannot generate a second action potential?

Answer 23

The refractory period is a direct consequence of Na⁺ channel inactivation.

Question 24

What happens when a voltage clamp recording is done on a cell that is depolarized?

Answer 24

There is an initial capactive current, a transient inward current, and a delayed outward current.

Question 25

True or False?:

According to Hodgkin & Katz: At rest, P_K : P_Na : P_Cl = 1 : 0.04 : 0.45. At the undershoot after the action potential, P_K : P_Na : P_Cl = 1.8 : 0.00 : 0.45.

Answer 25

True

Question 26

Are EPSPs inward (negative) or outward (positive) currents?

Answer 26

EPSPs are inward.

Question 27

Explain Na⁺ channel inactivation.

Answer 27

When triggered by a membrane depolarization, voltage-gated Na⁺ channels open, increasing the relative permeability of Na⁺, and allow Na⁺ ions to flow in along their concentration gradient. After they have been opened for a few milliseconds, they are inactivated (rather then closed) through a ball & chain model (a small protein configures itself to cover the opening of the protein). The channel stays inactivated until the membrane potential is restored to a low negative value around its resting potential, at which point it becomes closed again. This transition from open to inactivated to closed is the reason the refractory period exists.

Question 28

What is a current clamp? Why is it called a current clamp?

Answer 28

All voltage recordings are misleadingly referred to as current clamp. It is misleading because it is measurng voltage and current is in fact not clamped. It is simply called this to parallel voltage clamp recordings that measure current.

Question 29

What is wrong with this image?

Answer 29

Due to the hyperpolarization of the membrane potential, there is a large change in the driving forces of the ions. This is not going to open new channels, but it will cause more current to flow. As such, you should have a slight amount of inward current.

Question 30

What technique is visuaized below? What measurement is being recorded? What does it represent? What do the spikes on the graphs with capitance represent?

Answer 30

This is the voltage clamp technique. It is recording the measured current used to move the actual V_m to the command voltage. The current tells you how many ion channels are open at a given time. The spikes are from the voltage clamp amplifier compensating for the cell’s capacitance, but we don’t look at them in analysis (only the steady states are important).

Question 31

True or False?:

K⁺ channels become inactivated after they open.

Answer 31

False

Na⁺ channels become inactivated after they open.

Question 32

What property of axons does Na⁺ channel inactivation give rise to?

Answer 32

Channel inactivation gives rise to the directionality of information flow. An action potential is able to propagate down an axon by depolarizing the segment located distally from it without depolarizing the segment that it has already just propagated through.

Question 33

What did Bernstein’s membrane hypothesis state? Was his hypothesis correct?

Answer 33

Bernstein proposed a possible mechanism for Matteucci’s experimental results. He proposed that there’s an asymetric gradient of ions inside and outside of cells, the resting membrane is more permeable to K⁺ ions, and that the action potential is due to transient increases in permeability to all ions. He predicted that the action potential should be accompanied by an increased membrane conductance and that voltage should approach 0 mV at the peak of the action potential. Some of this is right and some of this is wrong.

Question 34

What are the 3 properties of ionic conductances during the action potential?

Answer 34

1. Na+ conductance is transient (rapidly inactivates). (Shown in middle five graphs.)
2. K+ conductance is delayed. (Shown in bottom five graphs.)
3. Both plateau at positive membrane potentials. (Shown in top two graphs.)

Question 35

What is an ion’s conductance a measure of?

Answer 35

An ion’s conductance is a direct measure of how many ion channes are open at a given time

Question 36

Are IPSPs inward (negative) or outward (positive) currents?

Answer 36

Outward