Practice exam answers/feedback

Which of the following correctly matches glia to their function?

Schwann cells myelinate axons in the PNS - Microglia scavenge dead cells. - Oligodendrocytes myelinate axons in the PNS. - Astrocytes recycle neurotransmitters. - Schwann cells form the myelin sheath around axons in the PNS. - Astrocytes form the blood brain barrier and are part of the tripartite synapse.

In an experiment, you stimulate an axon at some distance from the axon initial segment. Normally, the action potential can only travel away from the site of the stimulus. Which change might enable the action potential to travel back towards the initial site of the stimulus?

Shorten the absolute refractory period - Normally, the AP starts at the axon initial segment and travels down the axon, away from the stimulus because there are not many voltage-gated Na+ and K+ channels in the soma. The AP is not able to travel back to the AIS because the absolute refractory period prevents a region that just fired an AP from firing another AP. - If the absolute refractory period was short enough, depolarization in adjacent regions would be able to cause an AP

The threshold to open for the Kv2.1, Kv4.1, and HERG channels are all the same.

TRUE - The threshold to open are the same for all these potassium channels (-40 mV). This gives them identical conductance vs. Vm graphs.

Imagine a cell in which the equilibrium potential for Cl- is (-40) mV. The outside concentration for Cl- is INCREASED by 10 fold. What will the new ECl- be? Assume temperature = 19 deg C.

- 98 mV This question addresses the ten fold rule and the Nernst equation at 19 deg C: - Increasing outside Cl- 10 fold will increase Log [X]o/[X]i 10 fold - For chloride, 58/z = 58/-1 = (-58). - This means that a 10 fold increase in [Cl-]o will change ECl- by (-58 mV) - If you start at ECl- = (-40), the end will be (-40) + (-58) = (-98) mV

Which would cause the largest INCREASE in membrane potential (Vm)? Assume normal physiological conditions with Vrest = -60 mV and temperature = 19 deg. C.

- If you start at 19 deg C and Vm = (-60 mV), this means that the log portion of the equation has a negative value. Increasing temperature will increase RT/F (and it is positive). This means that Vm will DECREASE with increasing temperature - Doubling [K+]i will decrease the value of the log portion of the equation and DECREASE Vm - Doubling [Cl-]o will decrease the value of the log portion of the equation and DECREASE Vm - Doubling Pk will enable outward K+ current to influence Vm even more and bring Vm closer to EK of -70, thus DECREASING Vm

A cell has an extracellular Cl- concentration of 100 mM and an intracellular Cl- concentration of 10. What is the equilibrium potential for Cl- at 19 deg C ?

-58 mV

These channels are responsible for the cell's high potassium permeability at resting membrane potential.

2P K+ channels - 2P K+ leak channels have constant permeability to potassium (conductance is highest at pH 8). Remember that Vm approaches an ion's Ex when the membrane is permeable to that ion. This explains why Vrest is so close to potassium's Ex.

Which of the following channels would be MOST affected by respiratory acidosis, in which the pH of the body decreases?

2P K+ leak channels - The 2P K+ leak channels are most directly affected by pH, with a decrease in activity due to a drop in conductance at pH around 6. The other channels are not directly affected by pH.

Which of the following statements is/are true regarding driving force?

DF = EG + CG - It is possible to have DF when either EG or CG is zero. - At equilibrium potential for an ion DF = 0

Which of the following statements is FALSE?

Driving force requires both an electrical and chemical gradient - DF = CG + EG. To have DF, there must be either a CG or an EG. There can be DF when there are both CG and EG, but if CG and EG are equal and opposite, then there is DF= 0 - DF = Vm- Ex This means that DF increases as the difference between Vm and Ex increases.

What causes the absolute refractory period?

Inactivation of voltage-gated sodium channels - When sodium channels are closed but not inactivated, it is possible for another action potential to occur - Inactivation of the VG Na+ channels makes it impossible for another action potential to fire - Opening of VG Na+ channels causes the rising phase at the start of an action potential - Opening of VG K+ channels causes the falling phase and contributes to the relative refractory period, but not the absolute refractory period

Under normal biological conditions, how could a cell move its Vrest to +40mV?

Increase permeability to Na+ Increase outside concentration of K+ This question requires applying the Nernst and Goldman equations - The EK+ = -70 mV. Increasing permeability to K+ will bring Vm closer to EK (ie. DECREASE Vm) - The ENa+ = +50 mV. Increasing permeability to Na+ will bring Vm closer to ENa+ (ie. INCREASE Vm) - Increasing [K+]o will increase the log portion of the Nernst and Goldman equations and INCREASE Vm

How could you DECREASE the size of the stimulus that is required to fire an action potential during the relative refractory period?

Increase the outside concentration of K+ Make the voltage-gated K+ channels close faster - Because the EK+ is the lowest limit for the undershoot phase, increasing outside K+ would mean that the cell is less hyperpolarized during the relative refractory period and a smaller stimulus would be required to bring the cell to threshold. - The undershoot phase occurs because the voltage gated K+ channels are slow to close. Making them close faster would mean that the K+ current would be shut off sooner and the cell would not get as hyperpolarized (i.e. less undershoot).

If you applied scorpion beta toxin and voltage clamped a typical voltage-gated sodium channel, what might occur?

Inward current at -50 mV Conductance would be high at -40mV Transient current at -40 mV Beta toxin affects Na+ channels by decreasing threshold and making the channel open and pass current to flow at a lower Vm. - Na+ causes an inward current at these membrane potentials because Ex< Vm. - Beta toxin lowers threshold, so that the channel opens at Vm of about -120 mV and conductance is maximal at Vm= -40. - Na+ current would still be transient because the beta toxin does NOT affect inactivation

Which of the following channels would pass the most current at -100 mV?

KIR (K+ inward rectifying) channels - KIR channels are not voltage sensing, so they are always open but only pass inward K+ current. This inward current can only occur when the cell is below potassium's equilibrium potential of -70 mV, which occurs at -100 mV. Therefore, KIR will be active and passing inward current. All of the other channels are voltage sensing and will not be open at -100 mV

How do KV4.1 channels DIFFER from KV2.1 channels?

KV4.1 passes current transiently when voltage clamped above threshold - KV4.1 inactivates after opening and thus passes transient current

A person has a rare disease where some of their neurons are unable to produce ATP. Which process will be the most directly affected?

Moving Na+ and K+ ions via a Na+/K+ pump - The Na+/K+ pump requires ATP because it is moving two ions against their concentration gradients. Anti-porters and co-transporters do not require ATP because they are using energy from the electrochemical gradient by moving at least one ion with its electrochemical gradient. The opening of voltage-gated Na+ channels is not directly affected by ATP

____________ channels do NOT have an inactivation domain.

NaV channels KV4.1 HERG channels ALL THE ABOVE HAVE INACTIVATION DOMAINS All of these channels have inactivation domains: - NaV open at threshold and inactivate a few milliseconds later. Deinactivation and closing occurs when the channel returns below threshold - KV4.1 inactivation, deinactivation and closing are similar to NaV - HERG open at threshold and immediately inactivate. When the channel returns below threshold, HERG deinactivate, pass current for a few milliseconds, then close.

A beaker with two chambers and a selectively permeable barrier contains NaCl. The left side contains a low concentration of NaCl while the right side contains a high concentration. The barrier is permeable to Cl-. At equilibrium what is the direction of the electrical gradient on Cl-?

left to right - The concentration gradient is from right to left, and at equilibrium the DF = 0 so the electrical gradient must be equal and opposite (left to right) to the concentration gradient.

When Ex < Vm, current for a positive ion will be ____________ and current for a negative ion will be___________. Assume there is permeability for the ion.

outward; outward When Ex < Vm there will be a an outward current in order to DECREASE Vm.An outward current ALWAYS decreases Vm. This could be: - positive ion moving out of the cell - negative ion moving into the cell

What aspect of an Na+ channel confers its ion selectivity?

pore region

If Vm > Ex, there will be a movement of _____ ions _____ the cell

positive, out negative, in - There will be an outward current, which can either be positive ions moving out of the cell or negative ions moving into the cell to lower Vm to Ex.

scorpion beta toxin

shifts voltage dependent Na+ channel activation - Na+ channels open at potentials much more negative than normal (lowers the threshold of the VG Na+ channel) --> uncontrolled AP firing

Membrane potential is defined as

the charge inside versus outside.

During an action potential in a neuron, Na+ will have _____ inward current, and K+ will have _____ outward current.

transient; transient - During an action potential in a neuron, both channels have transient currents. This is because action potentials occur quickly, and more importantly, the flow of the ions has a significant effect on the membrane potential, which will cause changes in how the ion channels pass the ions. During a voltage clamp, the membrane potential is kept at the same value, so there is a sustained K+ current, but in a neuron, this outward flow of K+ decreases the Vm past a closing threshold for the K+ channels, and the channels will then close so that K+ produced only a transient current.

The voltage-gated sodium channel is mutated so that it de-inactivates more quickly than normal. How will the neuron be affected?

The absolute refractory period will be shorter than usual - The absolute refractory period is due to the inactivation of the Na+ channels. Therefore, if it takes less time to to de-inactivate, the absolute refractory period will be shorter.

A beaker with two chambers and a selectively permeable barrier contains NaCl. The left side contains a low concentration of NaCl while the right side contains a high concentration. The barrier is permeable to Cl-. At equilibrium, how is the chemical gradient for Cl- different from the chemical gradient at the start?

The chemical gradient is decreased compared to the start - The chemical gradient decreases as the electrical gradient increases moving towards DF = 0. But, there is still a chemical gradient because the electrical gradient becomes equal and opposite to it at equilibrium. The direction of the chemical gradient is the same as at the start

Which of the following is true for a 'typical' voltage-gated K+ channel? Assume EK+ = -70 mV

The conductance at 50 mV is greater than the conductance at 0 mV - VG K+ channels have a threshold around -40 mV and reach peak conductance roughly around 20 mV. There is still current at 0 mV and the driving force is outward at both 0 mV and 50 mV because the equilibrium potential of the channel is -70 mV.

Which of the following is FALSE about the current flowing through a single voltage gated Na+ channel that is patch clamped at +20 mV?

The current stays for the duration of the voltage clamp - The channel remains open for the duration of the voltage clamp: this is true with K+ channels but not Na+ channels. - The Na+ channels inactivate and stop passing current during the voltage clamp. Although we can determine the average amount of time a single channel will pass current, the exact amount of time a single channel passes current can vary.

Tetraethyl ammonium (TEA) is applied to a neuron to block voltage-gated potassium channels. The neuron is then voltage-clamped above the threshold and CURRENT is recorded. Compared to a recording at the same voltage clamp, but without TEA, which part of the current will change? HINT - think about how current and voltage plotted

The delayed outward - Remember: when we plot current, inward current goes down and outward current goes up. - In a voltage clamp above threshold, the Na+ channels open and inactivate early, causing a transient current that is inward due to the DF. If the Na+ channels are blocked, the early transient inward current would be eliminated. - The K+ channels take longer to open, but remain open, causing a sustained current that is outward due to the driving force. TEA would affect this part of the curve.

A neuron with nodes of Ranvier that are too far apart from each other can no longer faithfully propagate an action potential. Why?

The passive electrical signal in the axon beneath the myelin dissipates before it can reach the next node of Ranvier. - In myelinated axons, the VG channels are found at the Nodes of Ranvier that are unmyelinated. The active propagation of the AP involves the opening of the VG channels at the nodes. The current moves passively under the myelin. If the nodes are too far apart, the current will dissipate and be too low to bring the channel to a threshold at the next node.

A high concentration of KCl is placed on one side of a selectively permeable barrier and a low concentration is placed on the other side of the barrier. The barrier is only permeable to potassium (K+). What is the driving force on the potassium at equilibrium?

There is no driving force (DF = 0) - At equilibrium, the driving force on a permeable ion will be zero since the electrical gradient and concentration gradient will be equal and opposite

A high concentration of KCl is placed on one side of a selectively permeable barrier and a low concentration is placed on the other side of the barrier. The barrier is only permeable to potassium (K+). What is the electrical gradient on K+ and Cl-at the start?

There is no electrical gradient for either ion - at the start, there will be no electrical gradient for either ion because each positive charge from potassium (K+) will be cancelled out by the negative charge of the chloride (Cl-) since they came "paired" from the salt.

If the concentration of chloride outside the cell [Cl-]o is INCREASED, how does that affect Vm at rest?

decreases Vm a little - Keeping in mind the Goldman equation [Cl-]o is in the denominator, so increasing [Cl-]o will decrease Vm. At rest the membrane is only slightly permeable to Cl-, Vm will only change a little when [Cl-] changes.

If you voltage-clamp a neuron at +60mV, what type of current(s) will be detected?

early Na+ outward K+ outward Na+ Normal physiological conditions were given as EK+ = -70 ENa+= +50 @ a voltage clamp of +60 mV, Vm will be greater than both EK+and ENa+, so there will be OUTWARD current for Na+ and K+.The inactivation of the VG Na+ channel is independent of Vm, so the Na+ current will be transient.

A neuron has its cell body in the spinal cord and activates a neuron that it synapses on in the brain. This is an _____________________ neuron.

excitatory projection neuron - The keyword "activates" is used to describe an excitatory neuron. There are two clearly defined regions, and this neuron leaves one and enters the other, making this a projection neuron.

Multipolar neurons

have at least two dendrites have a single axon - Multipolar neurons typically have one axon and at least 2 dendrites. A neuron with 1 axon and 1 dendrite would be bipolar.

Which of the following would NOT increase the conduction velocity (i.e. speed) of and action potential down an axon?

increasing the length of the axon - Increasing the diameter of the axon and/or myelinating the axon will both increase the conduction velocity. This is why the fastest conducting axons in the mammalian nervous system are booth the thickest (i.e.have the greatest diameter) and are myelinated.

In the classical model of a voltage-dependent K+ channel, how many times does a single alpha subunit weave in and out of the membrane (i.e. how many transmembrane domains does it have)?

6 - A functional VG K+ channels requires 4 alpha subunits, each of which has 6 transmembrane domains. 4x6=24

Imagine that the Na+/K+ ATPase pump has consumed two ATP. This means that

6 Na+ have exited and 4 K+ have entered the cell. - Each round of sodium/potassium translocation by the Na+/K+ pump results in the consumption of one ATP molecule. ATP is used to move these ions against their gradient. Each round results in 3 Na+ leaving the cell and 2 K+ entering it. This is why [Na+] is higher outside and [K+] is higher inside. Two rounds have passed for two ATP to have been consumed, so 6 Na+ have exited and 4 K+ have entered the cell.

At rest, a neuron is depolarized.

FALSE Hyperolarized is Vm < Vrest Depolarized is Vm > Vrest - Therefore, at rest, the neuron is neither hyperpolarized nor depolarized.

Ions can only flow through a channel in one direction

FALSE The direction an ion moves is determined by the direction of the DF. - DF is inward if Ex>Vm - DF is outward if Ex<Vm

The direction of electrical current for a given ion ( Ix ) is dependent on which if the following

Ex Vm The reversal potential of ion "x" - The direction of Ix depends on the relationship between Ex and Vm.

Protein subunits are sections of a protein encoded by the same gene that differ in tertiary structure.

FALSE - A protein domain is a section of a protein from the same gene that have a different tertiary structure and function. A protein subunit, on the other hand, is another single protein that can assemble together with other proteins to form a quaternary structure. Protein subunits are not encoded by the same gene.

The probability that a single potassium channel is open is directly proportional to the driving force on the cannel.

FALSE - Driving force and conductance are independent of each other. You can have g without DF and vice versa.

A voltage-gated sodium channel has more alpha subunits than a KV1.4 channel.

FALSE - The VG-Na+ channels are made up of a single alpha subunit with four domains. A KV1.4 channel has 4 alpha subunits

The central nervous system contains all of the nerves found in the brain, head and neck

FALSE - The brain is part of the CNS, but the cranial nerves, which innervate the head and neck, are part of the peripheral nervous system (PNS).

The tripartite synapse involves which type of glia?

astrocytes - Astrocytes are the only glia involved in the tripartite synapse, where they surround a neuron's synapse and regulate the synaptic connection.

TEA

blocks K+ channels - slows (delays) repolarization, which leads to an increase in action potential duration and an increase in the effective refractory period

scorpion alpha toxin

blocks VG Na+ channel inactivation - if there was a NA+ current, it would last longer because it slows the inactivation of Na+ channels

Tetrodotoxin

blocks voltage-gated sodium channels - this means that there will be NO Na+ early current

Which of the following does NOT determine the direction of ion flow?

conductance - Driving force is the primary determiner or the direction of flow since it dictates which direction the ion "wants" to flow in. Since DF = CG + EG, both concentration gradient and electrical gradient contribute to the driving force, meaning they contribute to the direction of flow. Conductance is necessary for an ion to flow, but it does not determine the driving force itself

To have a current for ion X (IX) which of the following is/are required?

conductance for X - I = DF x g. - To have current, there must be driving force and conductance - To have a driving force, you must have either a chemical gradient, and electrical gradient, or both, but it is not required to have both