Question 1

A neuron's repetitive firing rate is limited by an absolute refractory period, during which a new action potential cannot be generated. Which event is chiefly responsible for this limit?

Accepted Answer

The inactivation of the voltage-gated Na⁺ channels delays the firing of the next action potential. The slow inactivation of the voltage-gated K⁺ channels also contributes to the refractory period.

Question 2

Aquaporin has a pair of key asparagine residues located on the wall almost halfway through its pore. These residues simultaneously bind to the oxygen atom of a passing water molecule, rendering it unavailable for hydrogen-bonding. As a result, …

Accepted Answer

The simultaneous hydrogen-bonding of the two Asn residues with the water molecule prevents the water molecule from participating in a proton "relay" that can result in the net transport of protons across the membrane.

Question 3

Which of the following graphs better represents the change in the relative conductance of Na⁺ and K⁺ channels during an action potential in a neuronal membrane?

Accepted Answer

The voltage-gated Na⁺ channels open quickly during an action potential and are then rapidly inactivated. The voltage-gated K⁺ channels open and close more slowly and repolarize the membrane potential.

Question 4

Which of the following is the reason why an aquaporin does not pass ions (such as Na⁺) through?

Accepted Answer

The pore in the aquaporin channel is not large enough to allow hydrated ions to pass. On the other hand, the hydrophobic wall of the pore makes it too unfavorable for an ion to dehydrate to enter the pore.

Question 5

Astroglial cells in the brain can actively import the amino acid glutamate from the synaptic cleft, convert it to the amino acid glutamine, and release the glutamine into the cleft to be subsequently taken up by the presynaptic neurons. The neurons then convert it back to glutamate. Why is this function of glial cells important?

Accepted Answer

The astroglial cells help deplete the neurotransmitter glutamate from synaptic clefts after its release from presynaptic axon terminals. These cells convert the neurotransmitter to the inert amino acid glutamine, which can then be released and taken up by the presynaptic cell to be converted back to glutamate and used during later synaptic transmissions.

Question 6

A potassium channel conducts K⁺ ions several orders of magnitude better than Na⁺ ions, because …

Accepted Answer

The selectivity filter in the potassium channel discriminates between the two ions very efficiently. The sodium ions cannot get rid of their water shell because they are too small to interact favorably with the pore.

Question 7

In a voltage-clamp experiment on a squid giant axon, the membrane potential is clamped at +20 mV, as shown below. Within the same time frame, which of the curves A to D better show qualitatively how the total membrane current changes? A positive value of the current represents an outward flow of cations.

Accepted Answer

The rapid opening of the sodium channels leads to sodium influx, i.e. a negative current. The slow opening of the potassium channels leads to potassium efflux, i.e. a positive current. The latter current persists as long as the voltage-gated K? channels stay open.

Question 8

Which of the following situations in a neuron results in action potentials that have extended depolarization phases?

Accepted Answer

If the inactivation mechanism in voltage-gated Na⁺ channels is compromised, the delayed closing of these channels would lead to an extended depolarization phase. A similar effect can be obtained by inhibiting the voltage-gated K⁺ channels.

Question 9

Indicate true (T) and false (F) statements below regarding ion channels in cellular membranes. Your answer would be a four-letter string composed of letters T and F only, e.g. TTTT.
( )	With patch-clamp recordings, it is possible to study ion transport through a single molecule of a channel protein.
( )	Cells that are not electrically excitable often lack gated ion channels in their plasma membrane.
( )	The aggregate current crossing a patch of plasma membrane represents the degree to which each individual channel is open at that time.
( )	Patch-clamp recordings have shown that any voltage-gated ion channel opens as soon as the membrane potential is altered.

Accepted Answer

The powerful patch-clamp technique can be used to record ion currents through a single ion channel. Using this technique, individual gated channels are observed to randomly flip between open and closed in an all-or-none fashion to generate the aggregate membrane current. Such experiments have also shown that even cells that are not electrically excitable have a variety of gated ion channels.

Question 10

The nicotinic acetylcholine receptor is an ionotropic receptor that can be activated by nicotine, a stimulant drug found in cigarettes. Additionally, ?-bungarotoxin, a neurotoxin found in the venom of some snakes, binds preferentially and tightly to the closed conformation of the receptors. Another drug, donepezil, is a potent acetylcholinesterase inhibitor used to treat patients with Alzheimer's disease. If applied at a neuromuscular junction, indicate whether each of the compounds (1) acetylcholine, (2) nicotine, (3) ?-bungarotoxin, and (4) donepezil would enhance (E) or suppress (S) the Ca²⁺influx in the muscle cells. Your answer would be a four-letter string composed of letters E and S only, e.g. EESS.

Accepted Answer

The Ca²⁺ influx in the muscle cell is stimulated by acetylcholine or nicotine through the opening of ionotropic acetylcholine receptors. Acetylcholinesterase lowers the concentration of acetylcholine at the neuromuscular junction, and its inhibitor would therefore also enhance Ca²⁺influx mediated by acetylcholine. In contrast, by favoring the closed state of the channels, ?-bungarotoxin suppresses the influx and can cause paralysis.

Question 11

MscS and MscL are mechanosensitive channels that ...

Accepted Answer

The mechanosensitive channels of small and large conductance (MscS and MscL) in bacteria open to form relatively nonselective pores of different sizes when the osmotic pressure increases to moderate and high levels, respectively.

Question 12

Voltage-gated cation channels in the plasma membrane of a neuron open when the membrane potential passes a threshold value that is about 20 mV above the resting potential. This corresponds to a change of about 4 × 10⁶ newtons per coulomb in the magnitude of the electric field across the membrane compared to the resting state. The tetrameric channels have a voltage-sensing helix S4 in each of their four subunits. Most S4 helices contain seven residues with positively charged side chains. The charge carried by each such residue is about 1.6 × 10-¹⁹ coulombs. By reaching threshold depolarization, what are the magnitude and the direction of the collective force that the four S4 helices in the channel experience as a result of the change in the electric field? The force that particles of charge q in an electric field E experience is calculated as F = q.E.

Accepted Answer

This is an oversimplified picture of the yet-to-be-elucidated gating process in these channels. There are 4 × 7 (= 28) positively charged residues in the four S4 helices combined, whose total charge would be 28 × 1.6 × 10-¹⁹ coulombs. As a result of the change in the electric field (by 4 × 10⁶ newtons per coulomb), the change in the force would be equal to:
(28 × 1.6 × 10-¹⁹ C) × (4 × 10⁶ N/C) = 1.8 × 10-¹¹ N = 18 pN
Since the membrane potential has become slightly depolarized, the change in the force is directed outward, tending to push the positively charged S4 helices more toward the extracellular leaflet. Note that the membrane is still polarized (negative inside) at the threshold potential and the electric field has not reversed yet.

Question 13

A certain neuron in a mouse brain is firing about 300 times per second, whereas almost all of its neighboring neurons are firing at much lower rates of only a few times per second. This implies that ...

Accepted Answer

Based in part on their firing pattern, neurons can be categorized into functionally different types. The firing properties of each neuron type are largely determined by the dynamic levels of depolarizing (Na⁺ and Ca²⁺) and hyperpolarizing (K⁺) channels, and are under homeostatic control.

Question 14

A membrane potential is plotted over time in the following graph. The Nernst equilibrium potentials for four ions (A to D) that affect the membrane potential in this system are indicated in the graph. What happened in the time period indicated by a question mark?

Accepted Answer

Opening of the channels conducting ion D brings the membrane potential down near the equilibrium potential for this ion.

Question 15

Myelination of axons in the peripheral nervous system …

Accepted Answer

Myelin sheath is made by Schwann cells around axons in peripheral nerves; it insulates these axons, massively improves their conduction, and confines the "expensive" excitation mechanisms to interspersed nodes along the axon.

Question 16

From left to right, indicate whether the transmitter-gated channels for (1) calcium, (2) chloride, (3) potassium, and (4) sodium at a chemical synapse usually open in response to excitatory (E) or inhibitory (I) neurotransmitters. Your answer would be a four-letter string composed of letters E and I only, e.g. EEIE.

Accepted Answer

Excitatory neurotransmitters open cation channels leading to sodium or calcium influx and postsynaptic membrane depolarization, whereas inhibitory neurotransmitters open potassium or chloride channels, suppressing firing by making depolarization harder.

Question 17

Once expressed in a neuron in the mouse brain and subjected to a flash of light, how does channelrhodopsin affect the membrane potential?

Accepted Answer

Channelrhodopsins are light-responsive cation channels that can be engineered to be expressed in specific neural cell types. Opening of these channels in response to light allows sodium ions to leak into the cells, raising the membrane potential to the point when voltage-gated Na⁺ channels open and further depolarize the membrane in an action potential.

Question 18

In neurons, the synaptotagmin-1 protein is localized to presynaptic axon terminals. When activated, it facilitates the fusion of neurotransmitter-containing synaptic vesicles to the plasma membrane, leading to neurotransmitter release into the synaptic cleft. Which of the following would you expect to directly activate synaptotagmin-1 for this function?

Accepted Answer

Synaptotagmin-1 is activated by binding to calcium which flows into the cell through voltage-gated Ca²⁺ channels upon the arrival of an action potential. This activation drives neurotransmitter release.

Question 19

If the extracellular concentration of sodium ions is artificially decreased for a neuron, …

Accepted Answer

The resting membrane potential mostly depends on the electrochemical potential of the potassium ion, whereas the action potential is more dependent on the sodium ion, and its peak is expected to be lowered if the extracellular sodium concentration is decreased.

Question 20

Neuromuscular transmission involves the sequential activation of several ion channels. Sort the following events to reflect the sequence leading to muscle contraction. Your answer would be a five-digit number composed of numbers 1 to 5 only, e.g. 12543. (A) Opening of voltage-gated Na? channels in the muscle cell plasma membrane. (B) Opening of Ca²⁺ release channels in the sarcoplasmic reticulum membrane. (C) Opening of ionotropic acetylcholine receptors on the muscle cell plasma membrane. (D) Opening of voltage-gated Ca²⁺channels in the T tubules. (E) Opening of voltage-gated Ca²⁺channels in the motor neuron.

Accepted Answer

This sequence of events connects the arrival of the action potential at the axon terminal at a neuromuscular junction to the calcium-dependent contraction of muscle fibers.

Quiz 11: Membrane Transport of Small Molecules and the Electrical Properties of Membranes