Lecture 2 - The Action Potential

Question 1

What are three pieces of evidence that let us know that sensory stimulus evokes electrical impulses?

Answer 1

1. Local anesthesia
2. Stroke (when neurons for a certain part of the body are damaged, that part of the body stops functionning)
3. Electrical stimulation (the firing of action potentials lets us know that something is touching us)

Question 2

What was Johannes Muller’s theory and why was it wrong?

Answer 2

He said that we would never be able to measure the speed of an action potential because it is much too fast like in the case of the speed of light. This was wrong since the Action Potential conduction is actually slower than the speed of light

Question 3

What is the rule concerning distance of stimulus, and the time needed to perceive that stimulus?

Answer 3

1. If the stimulus is close to the brain, perception occurs with little delay
2. If the stimulus is far from the brain, perception occurs with longer delay

Question 3

What did Hermann von Helmholtz do?

Answer 3

1. He calculated the motor nerve conduction speed in frogs by shocking the frogs at different distances from the muscle, and seeing how long it took the frog to react/have a muscle contraction
2. He also measure the sensory nerve conduction speed in humans by shocking their skin and different distances from the brain and seeing how long it took them to react (clench their teeth, etc.)

Question 4

What are the three different “times” involved in perceiving stimulus?

Answer 4

1. Afferent: Time for signal to move towards the NS
2. Efferent: Time for signal to move away from NS
3. Intra-cortical: Time for instruction to be given the body and cause a response

Question 5

What solution can be made in order to calculate the conduction speed of a sensory AP?

Answer 5

Disregard efferent and intra-cortical times because they are the same for both the ankle and the shoulder.

The equation is usually:
Conduction speed = (Distance traveled from skin to brain) / (Time)

But we can have it be:
Speed = (Distance from ankle to brain - Distance from shoulder to brain) / (Ankle time - Shoulder time)

Question 6

What is the Goldman-Hodgkin-Katz (GHK Equation) and how does it differ from the Nernst equation?

Answer 6

The Nernst equation gives use the equilibrium potential of ions, as it is hypothetical and considers the membrane to be permeable to just one ion

The GHK equation is much more realistic, and considers that the membrane is permeable to multiple ions

The equation is:

Question 7

What is the proportion of PK to PNa during an Action Potential?

Answer 7

Before threshold: PK = 24PNa
During the rising phase: PK=10PNa
End of rising phase: PNa=4PK

Question 8

What are the three steps leading up to the opening of voltage-gated sodium channels?

Answer 8

1. Sensory receptor activity
2. Depolarization
3. Voltage-gated sodium channels open

Question 9

What are the three possible phases that a voltage-gated sodium channel can have?

Answer 9

1. Closed (inactivation gate is opened, activation gate is closed)
2. Opened (inactivation gate is opened, activation gate is opened)
3. Inactivated (inactivation gate is close, activation gate is opened)

Question 10

What does the Rising Phase loop look like?

Answer 10

Fast positive feedback loop

DEPOLARIZE MEMBRANE POTENTIAL –> Voltage gated sodium channels open –> Na+ rushes into the cell (depolarizes) –> …

Question 11

What does the End of the Rising Phase look like?

Answer 11

Fast positive feed back loop ends

DEPOLARIZE MEMBRANE POTENTIAL –> Voltage gated sodium channels inactivate –> Na+ no longer rushes into the cell (depolarizes) –>…

Question 12

What are the three steps leading up to the opening of voltage-gated potassium channels?

Answer 12

1. Na+ entry into the cell (rising phase)
2. Depolarization
3. Creaky door i.e. the voltage gated potassium channel opens letting K+ out

Question 13

What do the End of the Action Potential/Falling Phase loops look like?

Answer 13

There is the End of Rising Phase loop, that connects to the Falling Phase loop through the DEPOLARIZES MEMBRANE POTENTIAL:

DEPOLARIZES MEMBRANE POTENTIAL –> Voltage-gated potassium channels open –> K+ slowly leaves the cell (hyperpolarizes) –>…

Question 14

Why, even at its peak, is the membrane potential of an AP not the equilibrium potential of sodium?

Answer 14

This is because, as the GHK equation explains to us, the neuron is never exclusively permeable to sodium and the potassium leak channels always have potassium leaving the cell, pulling the membrane potential away from ENa

Question 15

What does a refractory period create?

Answer 15

It creates a “one way street” for action potentials, making them have a unidirectional conduction

Question 16

What is an Absolute Refractory Period?

Answer 16

1. Sodium channels are completely inactivated
2. No new AP can be triggered at all

Question 17

What happens if the VgNaC are blocked?

Answer 17

An action potential cannot fire

Question 17

What is a Relative Refractory Period?

Answer 17

1. Some of the sodium channels have returned to their resting state, but not all of them, still leaving a possibility for another action potential to get fired with a strong enough stimulus
2. The constant potassium efflux that causes an AHP/undershoot, makes a strong stimulus necessary

Question 18

What happens if the VgKC are blocked?

Answer 18

An action potential’s falling phase back to resting potential will be much slower, and there will be no undershoot

Question 19

What is the benefit of a refractory period?

Answer 19

Allows a unidirectional action potential conduction away from point of origin

Question 20

What is the consequence of a refractory period?

Answer 20

It limits the amount of Action Potentials that can be fired (upper limit on AP firing rate)

Question 21

What part of the refractory period causes the unidirectional conduction?

Answer 21

Refractory Wake

Question 22

What happens if we inject sodium ions in the middle of a cell?

Answer 22

1. Depolarizations spreads on either side of the injection site
2. Two action potentials are fired moving in opposite ways,
3. Given that their RPs are behind them they can only move forward and not backwards towards the injection site

Question 23

What happens when two action potentials moving in opposite direction meet?

Answer 23

Each action potential will meet the refractory period of the other action potential and they will essentially cancel each other out (they cannot continue conducting further).

Question 24

Who invented the Voltage Clamp technique? And what did they discover?

Answer 24

Hodgkin and Huxley, and they discovered the ionic basis on an action potential

Question 25

What animal was used in the Voltage Clamp technique?

Answer 25

Hodgkin and Huxley used a squid giant axon

Question 26

How does a Voltage Clamp work?

Answer 26

Investigators will clamp the voltage of a squid giant axon to whatever they want and study the changes in K+ and Na+ conductance

Question 27

What does the rapid inward current represent?

Answer 27

Sodium entering (rising phase)

Question 28

What does the slow outward current represent?

Answer 28

Potassium leaving (falling phase)

Question 29

At +52 mV why did Huxley and Hodgkin notice that their voltage amplifier did not need to inject negative current?

Answer 29

+52 mV is the sodium equilibrium potential in the squid (so there was no sodium coming in)

Question 30

How was the current being injected discovered to be related to the ions conduction in the cell?

Answer 30

When negative current needed to be injected to match the desired voltage (Vc), it meant that the neuron was gaining positive charge

When positive current needed to be injected to match the desired voltage (Vc), it meant that the neuron was losing positive charge

Question 31

How did Huxley and Hodgkin verify their theory?

Answer 31

They manipulated the Na+ extracellular concentration to make sure that the inward current was a result of sodium entering the cell

Question 32

What are three examples of VGNaC blockers?

Answer 32

1. Local anesthetics likes lidocaine
2. TTX (found in pufferfish liver + ovaries), that cause paralysis of the respiratory system
3. STX (found in butter clams) causing numbness, paralysis, paresthesia (pins and needle sensation on skin)

Question 33

What is the difference between an Action Potential and a Receptor Potential?

Answer 33

An action potential is all or none whereas a receptor potential (like the ones in Merkel cells) is graded and does not have a threshold (gradually changes based on the intensity of the stimulus)