Neurobiolgy: The Action Potential

Front 1

What researchers characterized the action potential? What was their model system?

Back 1

A.L. Hodgkin and A.F. Huxley characterized the action potential. Their model system was the squid giant axon.

Front 2

What kind of electrophysiological technique did Hodgkin and Huxley use to characterize the action potential (i.e. what technique produces the iconic graph of the action potential?)? Why was this technique more advantageous than its alternative?

Back 2

The iconic graph of the action potential was an example of current clamp, and the dependent variable was voltage. Current clamp was more preferable to voltage clamp because current clamp (but not voltage clamp) allows you to observe the effect of ionic concentration on action potential behavior.

Front 3

How does manipulating the amplitude of the current affect the action potential?

Back 3

If the current (i.e. inward positive current) is clamped at a higher amplitude, it results in a greater frequency of action potential, but no change in the amplitude of the action potentials.

Front 4

What does the driving force refer to? What factor determines which ion has the greatest driving force at rest? During the rising phase of the action potential? What is the symbol for driving force? What is the equation?

Back 4

The driving force refers to the rate at which a certain ion will flow across a selectively permeable membrane. As permeability to that ion increases, that ion's driving force increases. At rest, potassium has the highest driving force. During the rising phase, sodium has the highest driving force. Driving force is Gion = Vm - Eion.

Front 5

How do Gk and Gna differ when at rest? How do they both change over the course of the action potential? Imagine the graph.

Back 5

At rest, Gk is higher than Gna because K+ has a higher driving force than Na+. In the rising phase of the action potential, Gna spikes briefly (corresponding to the opening of voltage-gated Na+ channels). Midway through the rising phase, voltage-gated K+ channels open, causing a prolonged spike of Gk.

Front 6

Compare the difference between the graphs for G,ion and I,ion over the course of the action potential and at rest. Explain why this is true?

Back 6

The graphs are the same for the action potential. The only difference is that Ik and Ina are are at the same level when at rest, unlike the Gion graph in which Gk is higher than Gna at rest. This is because there is very little current for either K+ or Na+, because both are at electrochemical equilibrium.

Front 7

Why is the membrane voltage -65mV at rest and +40mv at the peak of the action potential?

Back 7

The resting Vm is -65mv because the membrane is most permeable to K+, whose Eion is -80mv. The peak of the action potential is +40 because during the rising phase the membrane is most permeable to sodium, and the Vm approached the Eion of Na+, +52mv.

Front 8

What is the relationship between voltage and conductance for Na+ and K+?

Back 8

As holding voltage increases, the conductance for both Na+ and K+ increases. However, Na+ conductance peaks early and briefly, while K+ conductance peaks late and for a prolonged period.

Front 9

What experiments determined which ion was responsible for the characteristic currents of the action potential?

Back 9

Pharmacological studies involving the sodium-or-potassium channel antagonists determined that sodium was responsible for the brief, early influx of positive current, and potassium was responsible for the delayed, prolonged efflux of positive current.

Front 10

What drug blocks the potassium channels? What drug blocks the sodium channels?

Back 10

TTX blocks the Na+ channel.
TEA blocks the K+ channel.

Front 11

What is the primary difference between the voltage-gated K+ channel and the voltage-gated Na+ channel? Why is this significant?

Back 11

The voltage-gated K+ channel has only one gate, and the voltage-gated Na+ channel has 2 gates. When there are fewer gates, ions can flow through more rapidly.

Front 12

What 2 portions of each subunit on the voltage-gated sodium channel are relevant?

Back 12

The S4 portion is the voltage sensor. The S6 portion is the gate.

Front 13

What are the 4 states of the voltage-gated Na+ channels? Use the proper term for each of the gates?

Back 13

(1)Closed state- sub-threshold; not open.
(2) Open- after threshold reached; open for short period.
(3) inactivated by ball and chain; this is absolute refractory period.
(4) deactivation gate closes, displacing ball and chain, and initiating relative refractory period.

Front 14

What region of an ion channel is responsible for its selective permeability? What 2 factors determine the selectivity?

Back 14

The pore loop of an ion channel determines what ion it is selective for. The 2 factors that determine the selectivity are (1) the diameter of the pore, and (2) the type of charged amino acids on the pore's interior surface.

Front 15

What happens when researchers manipulated the extracellular sodium concentration, and then elicited an action potential? What happens when you remove all extracellular sodium and try to elicit an action potential?

Back 15

When the extracellular sodium concentration was reduced, it resulted in a (1) delayed, and (2) less depolarizing action potential. When there's no extracellular sodium, you observe an early current (due to voltage-gated Na+ channels) but it flows the wrong way, outside the cell.

Front 16

Describe the evolutionary history of voltage-gated and ligand-gated ion channels.

Back 16

Voltage-gated ion channels are evolutionarily ancient, and ligand-gated channels are a rather recent development.

Front 17

How many transmembrane domains does a voltage-gated sodium channel have?

Back 17

It has four transmembrane domains.

Front 18

How do transmembrane proteins remain anchored to the membrane? Give an example. What parts of the ion channels interacts with the anchors?

Back 18

Transmembrane proteins remained anchored to the membrane by intracellular and extracellular adhesion molecules. Ankyrin is an extracellular adhesion molecule. The beta-subunits mediate all the anchoring, while the alpha subunits accomplish all the filtering and ion flow.

Front 19

What is the selectivity filter? How does it differ from the gate.

Back 19

The selectivity filter is the spatial bottleneck in the ion channel. The selectivity filter maintains that only certain types of ions can enter the channel. The gate, by contrast, is an absolute bottleneck, beyond which no ion can pass when it is closed.

Front 20

What 2 functions does the alpha subunit mediate? What regions are implicated in these functions?

Back 20

The alpha subunit is (1) a filter (S6), and (2) a sensor (S4).

Front 21

What do M, H, and N refer to? What is tau? How does it correspond to refractory periods?

Back 21

M, H, and N are mathematical terms used in the Hodgkin-Huxley equations to represent the gates on the voltage-gated sodium and voltage-gated potassium channels. M and H are the 2 sodium channel gates; M is the activation gate, and H is the inactivation gate (ball and chain). N is the potassium channel gate. Tau is the time at which each of these variables reaches 63% of its maximum value. The H gate has a small tau, corresponding to the absolute refractory period.

Front 22

Describe the time course of the activation-inactivation of the voltage-gated sodium channel. What mediates this property?

Back 22

The voltage-gated sodium channel opens and closes very rapidly. This is due to the ball-and-chain mechanism.

Front 23

How did researchers demonstrate that activation and inactivation of the voltage-gated sodium channel were mediated by different processes?

Back 23

By applying the enzyme pronase, which cleaves the ball and chain's chain, you observe a prolonged sodium-associated influx, rather than the characteristically brief spike.

Front 24

Describe the selectivity and efficacy of the voltage-gated sodium channel.

Back 24

The voltage-gated sodium channel is slightly permeable to certain other cations like ammonium, but it is primarily permeable to sodium.

Front 25

What is Pna?

Back 25

Pna refers to the permeability of sodium (presumably during the rising phase of the action potential). Pna is the standard by which all other ion permeabilities are compared. Ion permeability ratio = Pion/Pna.

Front 26

What 2 factors determines the properties of different ionic currents?

Back 26

The (1) type of ion and (2) the type of ion channel determine the kind of current that will be observed. Even for the same ion though, 2 different channels will produce a different kind of current.

Front 27

What determines the different current/action potential properties of different types of neruons?

Back 27

The different suite of ion channels determines what currents and action potentials you'll observe in a given neuron.

Front 28

What is the strict definition of current?

Back 28

Current is the movement of POSTIVE CHARGE.

Front 29

What is passive decay? What 3 factors determine passive decay, and how do they do so? What is lamda?

Back 29

Passive decay refers to the decrease in current strength as a function of the distance from which it was originally generated. As distance from the generation point increases, current strength decreases. As the diameter of the axon increases, the rate of decay increases. As the resistance of the membrane decreases (i.e. more open ion channels), the rate of decay increases. Lamda is the distance rom the generation point where the current is 37% of its original strength.

Front 30

Draw the circuit model of the neuronal membrane. What 7 connections must be included?

Back 30

Draw the diagram, and compare to the drawing in my binder. The membrane capacitor, the passive K+ channel, the passive Cl- channel, the inward K+ flow of the pump, the outward Na+ flow of the pump, the voltage-gated sodium channel, and the voltage-gated potassium channel.

Front 31

Why do action potentials move in one direction?

Back 31

Action potentials move in only one direction because there is a refractory period that prevents them from back-propagating.

Front 32

Explain the usefulness of myelin in terms of passive decay. What is this phenomenon called?

Back 32

The myelin represents increased resistance across the membrane, so the current can travel longer distances without dissipating. This "jumping" of current across the axon without any apparent dissipation is known as saltatory conductance.