Excitability (L1)

Question 1

Cardiac vs Neuronal vs Skeletal muscle Action Potential (shape)

Answer 1

Cardiac: wide with plateau (especially ventricular)
Neuronal: sharp upstroke and quick repolarization
Skeletal Muscle: quick upstroke, repolarization slows near end

Question 2

Define sub threshold potential

Answer 2

Depolarization of the membrane which does not result in an action potential; appears as a little bump with no sudden sharp peak.

Question 3

Are subthreshold signals maintained?

Answer 3

No, they degrade over the length of the axon. We say they are nonregenerative

Question 4

What is the section of the action potential where the membrane potential goes below the baseline?

Answer 4

Hyperpolarizing afterpotential

Question 5

Do subthreshold potentials elicit an action potential?

Answer 5

No

Question 6

What is the length constant?

Answer 6

Lambda—this is the distance the signal can travel before degrading to 30% its usual strength

Question 7

Define membrane resistance

Answer 7

The resistance of membrane passage; in the context of the axon, this is thedensity of ion channels

Question 8

Define axial resistance

Answer 8

The intracellular resistance

Question 9

What is the equation for lambda

Answer 9

Lambda = sqrt(Rm/Ra)*(d/4)

Question 10

Neurons with __ (larger, smaller)__ lambdas potentiate signals better?

Answer 10

Large; the signal takes longer to dissipate.

Question 11

Axons can be extremely long, sometimes up to a meter in length. What is the mechanism behind the preservation of signals sent along these axons?
A.) Myelination (Increases Rm)
B.) Nodes of Ranvier
C.) Myelination (Decreases Rm)
D.) A and B
E.) C and B

Think about why this is the case before flipping the card.

Answer 11

D.) A and B

Increasing membrane resistance decreases conductance of ions (which keeps them in the axon and passing the signal along! However, there will be some decay of this due to internal resistance. We keep the signal going by concentrations of VG Na Channels in the Nodes of Ranvier

Question 12

Define Saltatory conduction

Answer 12

Action potentials will naturally degrade if not refreshed. This is done at Nodes of Ranvier where there are concentrations of sodium channels (this will raise the membrane voltage and the signal can be passed down the cell. Thus we say the action potential is saltatory because it is jumping from Node of Ranvier to Node of Ranvier, until the synapse.

Question 13

Conduction velocity in myelinated vs unmyelinated axons

Answer 13

Conduction velocity is significantly greater in myelinated axons.

Question 14

Neuronal channel conductance during action potentials - which part of the potential is responsible for sodium channels, which for potassium?

Answer 14

The upstroke is done by sodium channels (VG sodium channels let sodium in, raising membrane charge (depolarizing))

The downstroke is due to potassium channels (VG potassium channels let potassium OUT, making membrane less negative (repolarizing)

Question 15

What are the unique gating properties of VG Na channels that allow for action potential dynamics? Describe the gating process of the Na channels in detail.

Answer 15

voltage gated sodium channels have both a closed and an inactivation gate. During a more positive membrane potential, VG Na channels will open. Then, as membrane potential becomes increasingly positive, a special gate (called inactivation gate) will shut. This makes the channel absolutely unable to open again until the membrane repolarizes (becomes less positive) enough that the channel switches to the closed state, where it can be activated again

Question 16

What are the periods of absolute and relative refractory?

Answer 16

In absolute refractory, sodium channels CANNOT be opened again, no matter what stimulus is applied (inactivated state). In relative refractory, the sodium channels are in the closed state, so they CAN be activated, but the membrane is so negative that only a very strong stimulus will elicit an action potential.

Question 17

Tetrototoxin (TTX): What does it do (molecularly speaking), and what did Hodgkin & Huxley use it for?

Answer 17

TTX comes from puffer fish and is attracted by the negative charge in the sodium channels but it gets stuck.

Hodgkin and Huxley used it to block sodium current so they could reveal what part of a stimulus was due to other ions (in this case, potassium)

Question 18

What is the relationship between the membrane potential and sodium channel availability?

Answer 18

As the membrane potential rises, more sodium channels will be in the inactivated state. The curve which describes this property is called the availability curve, or the H-Infinity curve

Question 19

What would be the result of improper Na channel inactivation (more Na channels inactivated or less channels inactivated than there should be)

Answer 19

More channels inactivated: You have slow conductance, difficulty to fire AP’s, and a reduced slope of AP. Patients will present with muscle weakness, arrhythmias, slow conduction time

Less channels inactivated: In some rare gain of function mutations it is easier to fire an AP. This can lead to things such as long QT syndrome, as well as arrhythmias.

Question 20

Do VG potassium channels have a refractory period

Answer 20

No

Question 21

When Vg K channels open, what happens to the membrane potential?

Answer 21

It becomes less negative and trends toward the K nernst potential

Question 22

What is the result of elevated potassium (hyperkalemia) on membrane potential and the cell’s ability to fire action potentials?

Answer 22

The resting membrane potential will rise, due to a decreased gradient between outside and inside potassium concentrations shifting the nernst equilibrium. Due to the properties of Vg Na channels as described by the availability curve, this will mean more Na channels are inactivated. This has a depressive effect on the inward flow of Na (sodium conductance is slowed/decreased, and conduction slows as a result). This means it is quite hard to trigger an action potential, and if you trigger it the slope would be decreased and conduction of the signal would be reduced.

Question 23

How does plasma Ca affect Na channel availability?

Answer 23

Ca is able to bind to the Na channels on the extracellular side and act as a sensor. In hypercalcemia it binds near the channels on the membrane. Although the RMP is never affected, this still raises the threshold for the VG Na channels.

Question 24

What can alter the Ca concentration in plasma?

Answer 24

There are many Ca binding proteins in plasma. Protein folding is affected by pH, so blood pH affects free (ionized) vs bound calcium. In high pH (acidic conditions), less proteins can hold onto Ca, meaning you have hypercalcemia because more is free (ionized) in plasma. In low pH (alkalosis), more proteins can hold onto Ca, meaning you may have hypocalcemia because LESS calcium is free (ionized) in plasma (more is BOUND)

Question 25

What affect do hypercalcemia and hypocalcemia have on excitability?

Answer 25

Hypercalcemia leads to less excitable cells because it binds near VG Na channels and changes the threshold (increases it), making it harder to fire an action potential. Hypocalcemia does the opposite by lowering the threshold and leading to hyperexcitability.

Question 26

What are respiratory conditions which can lead to hypercalcemia and hypocalcemia

Answer 26

Respiration increases or decreases;

In hypoventilation, you’re retaining a lot of CO2. CO2 levels will correlate with HCO3 levels (which is going to equate to a higher blood acidity). that acidity will lead to more ionized (free) calcium.

In hyperventilation, you blow off too much CO2. CO2 levels correlating with HCO3 levels (equating to a reduced acidity here), we end up seeing less ionized (free) calcium, as more will be binding to plasma proteins.

Question 27

PSP vs Action potential

Answer 27

PSPs are post-synaptic potentiations; therefore they are all subthreshold signals. You need to summate a lot of them to generate an action potential. PSPs can also be excitatory or inhibitory and this will affect what ion channels are opening during it (so an inhibitory IPSP would actually be bringing the membrane FURTHER from an action potential).