Study Question Set: Neuronal Electrical Signaling

Membrane Potentials

Easy

1. What is a membrane potential? Generally what is its value at rest?
2. What ion creates the membrane potential and how?
3. What is it called when a cell’s membrane potential becomes more positive? More negative?

4. What are the two forces that act on ions? What is the sum of these forces called?

   1. For each of the following ions, describe the direction of the two forces when the cell is at rest: Sodium, Potassium, Chloride, Calcium

5. What maintains the relative concentration of ions on either side of the membrane? What ions does it exchange, and how many does it move for one ATP?

   1. (Optional): What are symporters and antiporters?

Advanced

1. What is the Nernst equation and what does the value we can calculate with it mean?

   1. (Optional): What are the relative concentrations of the following ions inside and outside of a neuron?: Sodium, Potassium, Chloride, Calcium
   2. (Optional): What are the Nernst values for the following ions?: Sodium, Potassium, Chloride, Calcium
2. Why is the resting membrane potential not equal to the Nernst value for potassium at cellular conditions?
3. What is the Golmann-Hodgkin-Katz equation? How does it improve on the Nernst equation as a mathematical model of the membrane potential?
4. The membrane is often compared to a capacitor. What does this mean? In what ways is the metaphor good or bad?
5. Describe the Na/K ATPase exchange cycle, including the binding, hydrolysis, and release of ATP, the binding and release of ions, and changes in conformational states.
6. Why is the Na/K ATPase an example of primary active transport? What other ion(s) are moved with primary active transport? What ion(s) are moved with secondary active transport?
7. Draw the I:V curve for potassium when only leaky-K channels are contributing to the cell’s permeability.

8. What equation represents the conductance of a particular ion across the cell membrane?

   1. (Optional): Why is this value 0 for sodium at rest? Why does it change for potassium during an action potential?
9. What equation can be used to find the current of a particular ion at a given point in time? (hint, use Ohm’s law)

Challenge Problems

1. If the thickness of a cell membrane increases (say through myelination or longer phospholipid tails), how would this affect the membrane potential? How would it affect the flow of ions?

Passive Conductance

Easy

1. What are excitatory and inhibitory post-synaptic potentials?
2. What does it mean when we say IPSPs and EPSPs are graded and decremental?

Advanced

1. What three factors influence how far a potential will passively travel in a neuron?
2. What is the length constant ($\lambda$), and how is it derived?
3. What is the time constant ($\tau$), and how is it derived?
4. What is the cable equation?
5. How does increased axon diameter increase the speed of action potential propagation?
6. How does myelination increase the speed of action potential propagation?

Ion Channels

Easy

1. What type of biomolecule are ion channels? (Sugars, Polynucleotides, Proteins, etc.)
2. Ion channels involved in action potentials are said to be selective, that is, they only allow one type of ion through. What feature of ion channels makes them selective based on charge? What feature makes them selective based on size?
3. What part of voltage-gated ion channels makes them sensitive to changes in voltage?
4. Some sodium channels inactivate. What does this mean? How does it usually happen?

Advanced

(Note 1: A comprehensive knowledge of enzyme kinetics, agonism/antagonism, protein conformational dynamics/folding, and other protein structure biochemistry is also recommended (and I can make a similar study set for this in the future))

(Note 2: For a more comprehensive look at ligand-gated channels, look at the section on neurotransmitters)

1. Ionized sodium is generally smaller than ionized potassium, but has a larger hydration shell due to its stronger electromagnetic field. How do selectivity filters in sodium- and potassium-specific ion channels work to only allow specific ions through the pore?

2. At high concentrations of ions, the kinetics of ion current through a single channel plateaus (saturates). What does this indicate about what happens as ions pass through a channel pore?

   1. (Optional): What enzyme kinetics value is equivalent to 1/2 the max current (I)? Is this value usually very high or very low? What does this indicate about the affinity of pore-lining residues for the ions they shuttle?
3. Draw the I:V curve for an ohmic channel and an inwardly-rectifying channel.
4. Describe the structure of an individual voltage-gated potassium channel subunit. How many trans-membrane domains does it have? Which domains line the pore, and which domain is the voltage sensor? Where is the pore loop found?
5. Describe the supramolecular structure (quaternary structure) of a voltage-gated potassium channel (note that the structure is the same for sodium except that its subunits are linked by peptide bonds).
6. What feature of the voltage-sensor domain allows it to respond to changes in membrane potential?
7. What part of the voltage-gated potassium channel is thought to control its opening kinetics? (making it open later)
8. Describe the canonical model for voltage-gated sodium channel inactivation.
9. Describe the tertiary and quaternary structure of a standard inward-rectifying K+ channel and a K2P channel.
10. Describe the kinetics of fast- and slow-type inactivation (association speed, dissociation speed).
11. Describe C-type inactivation and N-type inactivation. Which type is commonly fast-inactivation, which type is slow-inactivation?

Action Potentials (Active Conductance and Propagation)

Easy

1. What is a threshold potential?
2. What part of the cell initiates an action potential?
3. What does it mean when we say an action potential is “all-or-nothing”?

4. What happens to cause the rising phase of an action potential? The falling phase?

   1. (Optional): Describe the flow of ions during the rising, falling, and hyperpolarized phases.
5. What happens at the peak of the rising phase?
6. Why does the cell hyperpolarize after the falling phase?
7. What is a refractory period? What is the difference between the absolute and relative refractory periods?
8. What is saltatory conduction? Why does it happen?
9. As an action potential propagates down the axon, what stops it from moving backwards?

Advanced

1. How do you experimentally isolate the current through voltage-gated sodium channels?
2. Draw the I:V curve for a voltage-gated sodium channel.
3. How do you find the conductance of a voltage-gated sodium channel given its I:V curve?
4. What equation gives the instantaneous conductance for an ion based on current and voltage?
5. How do you experimentally isolate the current through voltage-gated potassium channels?
6. Draw the I:V curve for a voltage-gated potassium channel.
7. Draw the conductance/time curves for sodium and potassium through voltage-gated channels.