Test Questions & Answers Ch.5 Structure Of Ion Channels 6e - From Neuron to Brain 6e | Test Bank Martin by A. Robert Martin. DOCX document preview.
Chapter 5: Structure of Ion Channels
Test Bank
Type: multiple choice question
Title: Chapter 05 - Question 01
1. A nicotinic acetylcholine receptor is activated by
Feedback: Subhead: Ligand-Activated Channels
Learning Objective: Describe how a nicotinic acetylcholine receptor (nAChR) is activated and allows ion flux through the channel.
Bloom’s Level: 1. Remembering
a. ACh.
b. muscarine.
c. intracellular messenger systems.
d. -bungarotoxin.
e. serotonin.
Type: multiple choice question
Title: Chapter 05 - Question 02
2. ACh, the ligand, only binds to at -subunits, which are 2 of the 5 subunits that comprise a nAChR yet conformational changes occur throughout its tertiary and quaternary structure. Why?
Feedback: Subhead: Ligand-Activated Channels
Learning Objective: Describe how a nicotinic acetylcholine receptor (nAChR) is activated and allows ion flux through the channel.
Bloom’s Level: 4. Analyzing
a. Ligands span between αγ and αγ-subunits so in fact 4 of the 5 subunits are affected.
b. Subunits interact via amino acid chains connecting their intramembrane regions, so movement in one subunit influences the others too.
c. β-subunits drive movement for all other subunits exclusively via M2-M3 connecting loops.
d. Via subunits tilting away from the axis of the receptor.
e. Regardless of how many ligands bind, all subunits have M2 helices that move within the membrane.
Type: multiple choice question
Title: Chapter 05 - Question 03
3. Which modifications reduce receptor conductance?
Feedback: Subhead: Ligand-Activated Channels
Learning Objective: Describe how a nicotinic acetylcholine receptor (nAChR) is activated and allows ion flux through the channel
Bloom’s Level: 4. Analyzing
a. substitution of 2′ threonine (T) with a smaller hydrophilic residue
b. substitution of 2′ threonine (T) with a larger hydrophilic residue
c. substitution of 2′ threonine (T) with a smaller hydrophobic residue
d. substitution of 2′ threonine (T) with any polar residue
e. substitution of 2′ threonine (T) with a larger hydrophobic residue
Type: multiple choice question
Title: Chapter 05 - Question 04
4. Charged amino acid residues located at cytoplasmic and extracellular surfaces of the receptor
Feedback: Subhead: Ligand-Activated Channels
Learning Objective: Describe how a nicotinic acetylcholine receptor (nAChR) is activated and allows ion flux through the channel
Bloom’s Level: 3. Applying
a. enable homomultimeric α7 channels even when other subunit isotypes are not present.
b. influence affinity for the bound ligand.
c. influence channel open time.
d. govern cation or anion selectivity of the channel.
e. govern ligand selectivity (e.g., serotonin, glutamate, γ-aminobutyric acid, glycine, or zinc).
Type: multiple choice question
Title: Chapter 05 - Question 05
5. Which type of information below helped determine the subunit composition and stoichiometry of nAChRs?
Feedback: Subhead: Ligand-Activated Channels
Learning Objective: Describe the physical structure of an nAChR.
Bloom’s Level: 4. Analyzing
a. Position of ligand binding sites at α-γ and α-δ interfaces
b. Affinity for α-bungarotoxin
c. Electron imaging and other physical techniques
d. Molecular weight of the purified Torpedo nAChR and its constituent subunits
e. More diameter and relative selectivity of large cations
Type: multiple choice question
Title: Chapter 05 - Question 06
6. Hydrophobicity of amino acid residues informs which property of nAChRs?
Feedback: Subhead: Ligand-Activated Channels
Learning Objective: Describe the physical structure of an nAChR.
Bloom’s Level: 2. Understanding
a. Their primary structure, i.e., amino acid sequence
b. Secondary and tertiary structure: membrane insertion of alpha helices
c. Secondary and tertiary structure: configuration of intracellular loops
d. Secondary and tertiary structure: ligand-binding site(s)
e. Quaternary structure: arrangement of subunits
Type: multiple choice question
Title: Chapter 05 - Question 07
7. Which subunits from vertebrate nAChRs, when their mRNA is expressed in oocytes, may be form homomultimeric channels?
Feedback: Subhead: Ligand-Activated Channels
Learning Objective: Describe the physical structure of an nAChR.
Bloom’s Level: 1. Remembering
a. Any α2–α10
b. Any α2–α6, α10
c. Any α7, α8, or α9
d. Any β2–β4
e. Any α2–α6, α10 with any of β2, β3, or β4
Type: multiple choice question
Title: Chapter 05 - Question 08
8. A sequence of 24 hydrophobic amino acids at the amino tail of the nAChR subunit ensures
Feedback: Subhead: Ligand-Activated Channels
Learning Objective: Describe the physical structure of an nAChR.
Bloom’s Level: 3. Applying
a. that ligand binding occurs principally on the α-subunit (and not β, γ, or δ).
b. M1-M4 transmembrane domains align in parallel.
c. that nAChRs can dimerize.
d. that the first transmembrane domain (M1) forms an helix as required for intercalation in the membrane.
e. that ligand-binding sites reside extracellularly.
Type: multiple choice question
Title: Chapter 05 - Question 09
9. Why was the electric organ of the ray Torpedo key in the structural characterization of nAChRs?
Feedback: Subhead: Ligand-Activated Channels
Learning Objective: Describe the physical structure of an nAChR.
Bloom’s Level: 2. Understanding
a. It provided sufficient quantities for biochemical isolation of the receptor.
b. Its receptors have unique affinity for α-bungarotoxin.
c. Compared to vertebrates, Torpedo receptors have a greater diversity of subunits that comprise the receptor and thus provide a wider spectrum of possible tertiary structures.
d. Its receptors are uniquely nicotinic whereas vertebrate receptors which can be nicotinic or muscarinic.
e. The tertiary structure of its subunits is equivalent to that of vertebrate receptors.
Type: multiple choice question
Title: Chapter 05 - Question 10
10. Why do we refer to the nAChR as a receptor rather than a channel?
Feedback: Subhead: Ligand-Activated Channels
Learning Objective: Describe the physical structure of an nAChR.
Bloom’s Level: 2. Understanding
a. To distinguish it from muscarinic receptors, which do not form a channel
b. Because it is present in skeletal muscle and electric organs (a modified form of muscle) as well as neurons
c. Because its principal function is reception of signals from presynaptic partners
d To emphasize its commonality with other Cys-loop receptors and dissimilarity compared to voltage-activated ion channels
e. Because its ligand-binding properties more substantively contributed to its characterization than the conduction properties of its channel
Type: multiple choice question
Title: Chapter 05 - Question 11
11. Positively charged arginines within the long intracellular loop connecting M3 and M4 dramatically influence channel conductance of which Cys-loop receptor?
Feedback: Subhead: A Receptor Superfamily
Learning Objective: Explain what distinguishes the superfamily of Cys-loop receptors, and name four members of the superfamily.
Bloom’s Level: 1. Remembering
a. The glutamate (GluCl) receptor
b. The serotonin (5-HT3) receptor
c. The γ-aminobutyric acid (GABAA) receptor
d. The glycine receptor
e. ZAC, the zinc receptor
Type: multiple choice question
Title: Chapter 05 - Question 12
12. Which of the following is an invertebrate anion channel?
Feedback: Subhead: A Receptor Superfamily
Learning Objective: Explain what distinguishes the superfamily of Cys-loop receptors, and name four members of the superfamily.
Bloom’s Level: 1. Remembering
a. MOD-1 receptor
b. EXP-1 receptor
c. GluCl receptor
d. GABAA receptor
e. Glycine receptor
Type: multiple choice question
Title: Chapter 05 - Question 13
13. Which of the following ligands gates inhibitory synaptic transmission in vertebrate and invertebrate nervous systems?
Feedback: Subhead: A Receptor Superfamily
Learning Objective: Explain what distinguishes the superfamily of Cys-loop receptors, and name four members of the superfamily.
Bloom’s Level: 2. Understanding
a. Serotonin
b. γ-aminobutyric acid
c. Glycine
d. γ-aminobutyric acid and glycine
e. Zinc
Type: multiple choice question
Title: Chapter 05 - Question 14
14. 5-HT3 receptors and nAChRs share which of these properties?
Feedback: Subhead: A Receptor Superfamily
Learning Objective: Explain what distinguishes the superfamily of Cys-loop receptors, and name four members of the superfamily.
Bloom’s Level: 3. Applying
a. The ligand that binds to them
b. Which ion(s) they conduct
c. Heterogeneity of subunits comprising them
d. Their expression in both vertebrate and invertebrate nervous systems
e. Their expression in both skeletal muscle and the nervous system cells
Type: multiple choice question
Title: Chapter 05 - Question 15
15. Modifying the primary structure of a receptor encapsulates which of the following techniques?
Feedback: Subhead: A Receptor Superfamily
Learning Objective: Describe three techniques that have been essential in determining the relations between receptor structure and function.
Bloom’s Level: 2. Understanding
a. Site-directed mutagenesis
b. Receptor expression in Xenopus oocytes
c. Electrical recording of single-channel or whole-cell receptor currents
d. Ligand binding affinity and pharmacology
e. Replacement of polar amino acids with nonpolar ones
Type: multiple choice question
Title: Chapter 05 - Question 16
16. Modification of the primary structure of a receptor encapsulates which of the following?
Feedback: Subhead: A Receptor Superfamily
Learning Objective: Describe three techniques that have been essential in determining the relations between receptor structure and function.
Bloom’s Level: 2. Understanding
a. Site-directed mutagenesis
b. Receptor expression and subunit assembly in Xenopus oocytes
c. Electrical recording of single-channel or whole-cell receptor currents
d. Ligand binding affinity and pharmacology
e. Replacement of polar amino acids with nonpolar ones
Type: multiple choice question
Title: Chapter 05 - Question 17
17. What technique allowed scientists to view nAChRs in their open state?
Feedback: Subhead: A Receptor Superfamily
Learning Objective: Describe three techniques that have been essential in determining the relations between receptor structure and function.
Bloom’s Level: 1. Remembering
a. Biochemical purification of the receptor from Torpedo
b. Plunge freezing
c. Site-directed mutagenesis
d. Photo-labeling (i.e., ultraviolet flashes) in the presence of Tritiated chloropromazine.
e. Cysteine screening followed by MTSEA exposure
Type: multiple choice question
Title: Chapter 05 - Question 18
18. Maximal channel current in nAChRs depends on
Feedback: Subhead: A Receptor Superfamily
Learning Objective: Explain the role of the M2 helices in the gating of Cys-loop receptors.
Bloom’s Level: 4. Analyzing
a. leucine and valine at 9′, 13′, and 16′ in the M2 helix.
b. hydrophobic isoleucine adjacent to lipid or other parts of the protein’s secondary or tertiary structure.
c. substitution of serine at 6′ in the M2 helix with a more hydrophilic amino acid.
d. substitution of serine at 6′ in the M2 helix with a more hydrophobic amino acid.
e. hydrophilic serine at 6′ in the M2 helix.
Type: multiple choice question
Title: Chapter 05 - Question 19
19. With respect to the structure and function of nAChRs, cysteine scanning
Feedback: Subhead: A Receptor Superfamily
Learning Objective: Explain the role of the M2 helices in the gating of Cys-loop receptors.
Bloom’s Level: 3. Applying
a. provided binding sites for tritiated chlorpromazine in the M2 helix.
b. refers to scanning for radioactivity of tritiated chlorpromazine after it reacts with cysteines in the M2 helix.
c. provided novel binding sites for QX222 in the open channel compared to existing QX222 biding sites in the native receptor.
d. revealed that amino acids at 2′, 3′, 6′, 8′, 9′, 10′, 13′, and 16′ lined the pore-forming side of the M2 helix.
e. revealed that amino acids at 2′, 6′, and 9′ lined the pore-forming side of the M2 helix.
Type: multiple choice question
Title: Chapter 05 - Question 20
20. Which of the following voltage-activated sodium channels is expressed in cells of both the peripheral and central nervous system?
Feedback: Subhead: Voltage-Activated Channels
Learning Objective: Name three types of voltage-activated channels and describe their functional properties.
Bloom’s Level: 1. Remembering
a. NaV 1.3
b. NaV 1.4
c. NaV 1.5
d. NaV 1.6
e. NaV 1.7
Type: multiple choice question
Title: Chapter 05 - Question 21
21. Why were electric eels used to discover nAChRs and voltage-activated sodium channels but not voltage-activated potassium channels?
Feedback: Subhead: Voltage-Activated Channels
Learning Objective: Name three types of voltage-activated channels and describe their functional properties.
Bloom’s Level: 5. Evaluating
a. nAChRs and voltage-activated sodium channels in eels are similar in structure and function to vertebrate channels so they make a good model to understand channels across phylogeny.
b. Electric eels provide an abundance of channels for biochemical purification prior to sequencing and cloning, but voltage-activated potassium channels were cloned using a different strategy.
c. A-type voltage-activated potassium channels are not expressed in electric eels, whereas those A-type channels are expressed in invertebrate Drosophila (fruit flies).
d. Electric eels are aquatic organisms and thus sensitive to toxins like α-bungarotoxin, TTX, and STX, which assist in biochemical purification.
e. Shaker-type mutants were a fortuitous discovery that facilitated biochemical purification of voltage-activated potassium channels thus obviating the need an eel-like model system with abundant channels.
Type: multiple choice question
Title: Chapter 05 - Question 22
22. The α-subunit of the voltage-activated potassium channel resembles
Feedback: Subhead: Voltage-Activated Channels
Learning Objective: Describe the physical structure of a voltage-activated channel.
Bloom’s Level: 2. Understanding
a. the α-subunit of the voltage-activated sodium channel.
b. the P-loop of the voltage-activated sodium channel.
c. domain IV of the voltage-activated sodium channel.
d. the α-subunit of the voltage-activated calcium channel.
e. the α-subunit typical of a Cys-loop receptor.
Type: multiple choice question
Title: Chapter 05 - Question 23
23. Which of the following characteristics are similar for Cys-Loop and voltage-activated sodium channels?
Feedback: Subhead: Voltage-Activated Channels
Learning Objective: Describe the physical structure of a voltage-activated channel.
Bloom’s Level: 2. Understanding
a. Relative size and molecular mass of their -subunits
b. Relative size and molecular mass of their β-subunits
c. The total number of membrane-spanning segments per subunit or domain
d. Structure of Cys-Loop receptor subunits and sodium channel domains I-IV
e. Primary structure of M2 helices in Cys-Loop receptors and S4 regions of sodium channels
Type: multiple choice question
Title: Chapter 05 - Question 24
24. Which of the following characteristics are similar for voltage-activated sodium channels and voltage-activated calcium channels?
Feedback: Subhead: Voltage-Activated Channels
Learning Objective: Describe the physical structure of a voltage-activated channel.
Bloom’s Level: 3. Applying
a. Selectivity of their pore regions
b. Voltage sensitivity and persistence of activation
c. Their position and function of their associated β-subunits
d. Prevalence of glycosylation sites in functional channels
e. The primary sequence similarity of their α-subunit and equivalent structure of domains I-IV
Type: multiple choice question
Title: Chapter 05 - Question 25
25. What senses membrane potential in voltage-activated channels?
Feedback: Subhead: Voltage-Activated Channels
Learning Objective: Explain the role of the S4 and S6 helices in voltage-activated gating.
Bloom’s Level: 2. Understanding
a. Arginine and lysine residues on the S4 transmembrane segment
b. Glycosylation sites ubiquitous on the α-subunit
c. Auxiliary β-subunits
d. The moderately hydrophobic P-loop region
e. Positively charged residues of the S6 transmembrane segment
Type: multiple choice question
Title: Chapter 05 - Question 26
26. m1 and m2 of KCS channels most closely mimic
Feedback: Subhead: Voltage-Activated Channels
Learning Objective: Explain the role of the S4 and S6 helices in voltage-activated gating.
Bloom’s Level: 3. Applying
a. M1 and M2 of nAChRs.
b. S1 and S2 of voltage-activated channels.
c. S4 of voltage-activated channels.
d. S5 and S6 of voltage-activated channels .
e. the extracellular loop connecting S5 and S6 of voltage-activated channels.
Type: multiple choice question
Title: Chapter 05 - Question 27
27. Opening a voltage-gated channel generally involves which of the following roles for S6?
Feedback: Subhead: Voltage-Activated Channels
Learning Objective: Explain the role of the S4 and S6 helices in voltage-activated gating.
Bloom’s Level: 2. Understanding
a. Forming the ion selectivity filter in combination with S5 and the S5-S6 linker region
b. Sensing transmembrane depolarization via its positively charged amino acids
c. Relieving the physical constraints that block the cytoplasmic mouth of the channel
d. Displacement within in the membrane via interactions with voltage-detecting S4
e. Possibly none: a large body of evidence shows that activation of channel currents can occur independently of an S4-coupled gating mechanism, which casts doubt on the role of S6, too
Type: multiple choice question
Title: Chapter 05 - Question 28
28. Where is the ion selectivity filter located, considering the quaternary structure of a representative, well-studied ion channel like KCS?
Feedback: Subhead: Voltage-Activated Channels
Learning Objective: Explain what role the P-loop plays in voltage-activated channels.
Bloom’s Level: 3. Applying
a. The outer vestibule of the channel, which is approximately 2 nm in diameter
b. Adjacent to short helices and their neighboring residues, which form a box-like structure at the channel’s extracellular face
c. Within the central pore
d. Within the lower pore
e. By the inner helix, which predominantly forms the narrowest part of the channel structure
Type: multiple choice question
Title: Chapter 05 - Question 29
29. Which statement summarizes how the 0.3 nm selectivity filter of KCS channels enables potassium to penetrate but not sodium or lithium?
Feedback: Subhead: Voltage-Activated Channels
Learning Objective: Explain what role the P-loop plays in voltage-activated channels.
Bloom’s Level: 4. Analyzing
a. Because of their smaller diameter and charge, sodium and lithium ions interact strongly with carbonyl oxygens and effectively get stuck in the pore region and do not flow through the channel.
b. Because their diameters exceed 0.3 nm, sodium and lithium are excluded on the basis of size.
c. Carbonyl oxygens provide a surrogate environment that keeps potassium ions in aqueous solution while passing through the channel.
d. Carbonyl oxygens provide a surrogate environment for dehydrated potassium ions in the selectivity filter that mimics the hydration energy of ions in solution.
e. Carbonyl oxygens provide a surrogate environment for dehydrated sodium or lithium ions in the selectivity filter that mimics the hydration energy of ions in solution.
Type: multiple choice question
Title: Chapter 05 - Question 30
30. In voltage-activated channels, preferential ion selectivity for calcium over sodium is governed by which of these factors?
Feedback: Subhead: Voltage-Activated Channels
Learning Objective: Explain what role the P-loop plays in voltage-activated channels.
Bloom’s Level: 3. Applying
a. Cumulative negative charge of amino acids that line the pore
b. An ensemble mix of negative, positive, and neutral amino acids that line the pore
c. Glutamine residues at four positions that line the pore
d. Aspartate followed by glutamate—that pattern repeated twice—at four key positions that line the pore
e. Characteristic features of the P-loop
Type: multiple choice question
Title: Chapter 05 - Question 31
31. What is the principal mechanism of inactivation in voltage-activated channels?
Feedback: Subhead: Voltage-Activated Channels
Learning Objective: Explain what happens when a voltage-activated channel is inactivated.
Bloom’s Level: 1. Remembering
a. Occlusion by elements of the ion channel that do not lie within the membrane
b. S6 helix closing off the cytoplasmic mouth of the channel
c. Displacement of S4 back to its “resting” position within the membrane
d. Inactivation, or current “switching off,” of the P-loop, possibly involving the selectivity filter
e. Displacement f S6 back to its “resting” position within the membrane
Type: multiple choice question
Title: Chapter 05 - Question 32
32. Piezo 1 is likely to transduce which of the following stimuli or senses?
Feedback: Subhead: Mechanoreceptor Channels
Learning Objective: Name two types of mechanoreceptor channels.
Bloom’s Level: 4. Analyzing
a. Sound (pitch) b. Body orientation (position with respect to gravity) c. Touch (e.g., pressure applied to the skin) d. Interoception
e. Heat
Type: multiple choice question
Title: Chapter 05 - Question 33
33. Deafness is associated with genetic knockout of which gene?
Feedback: Subhead: Mechanoreceptor Channels
Learning Objective: Name two types of mechanoreceptor channels.
Bloom’s Level: 1. Remembering
a. Transmembrane Channel-like Protein 1 (TMC1) b. Transmembrane Channel-like Protein 2 (TMC2) c. Tetraspan Membrane Protein of Hair Cell Cilia (TMHS) d. Transmembrane Inner Ear Protein (TMIE) e. Both TMC1 and TMC2
Type: multiple choice question
Title: Chapter 05 - Question 34
34. Which structural property is common among glutamate receptors and KCS potassium channels?
Feedback: Subhead: Other Channels
Learning Objective: Explain why glutamate receptors are so abundant in the CNS.
Bloom’s Level: 4. Analyzing
a. Ion selectivity of the pore
b. The number of transmembrane segments that comprise the receptor/channel
c. A small helical region between transmembrane segments that forms the pore
d. Positively charged amino acids located at every third position in one of the transmembrane domains
e. The pore region located on the cytoplasmic side of the receptor/channel
Type: multiple choice question
Title: Chapter 05 - Question 35
35. Imagine that you discover a new brain nucleus and its constituent neurons excite their downstream postsynaptic neighbors. Which of the following receptors are most likely to be expressed by the postsynaptic neighbors?
Feedback: Subhead: Other Channels
Learning Objective: Explain why glutamate receptors are so abundant in the CNS.
Bloom’s Level: 4. Analyzing
a. Nicotinic ACh receptors
b. Serotonin (5-HT3) receptors
c. γ-aminobutyric acid (GABAA) receptors
d. Glycine receptors
e. AMPA receptors
Type: multiple choice question
Title: Chapter 05 - Question 36
36. Which of the following factors gates present at the cytoplasmic side of the channel gates outward current flow in Kir channels?
Feedback: Subhead: Other Channels
Learning Objective: Explain the function of inwardly rectifying potassium channels.
Bloom’s Level: 1. Remembering
a. β-subunits
b. A relatively long carboxy tail that inactivates the channel like in voltage-activated sodium channels
c. Calcium
d. Magnesium
e. Intracellular biochemical messengers
Type: multiple choice question
Title: Chapter 05 - Question 37
37. A mammal senses painful heat on its skin. Which is the most likely channel transducing the stimulus?
Feedback: Subhead: Other Channels
Learning Objective: Name four different types of stimuli to which transient receptor potential (TRP) channels respond.
Bloom’s Level: 2. Understanding
a. Piezo 2
b. TRPV1
c. TRPM8
d. Kir
e. NaV 1.7
Type: multiple choice question
Title: Chapter 05 - Question 38
38. A mammal is drinking cold water from a stream Which is the most likely channel transducing the stimulus?
Feedback: Subhead: Other Channels
Learning Objective: Name four different types of stimuli to which transient receptor potential (TRP) channels respond.
Bloom’s Level: 2. Understanding
a. Piezo 2
b. TRPV1
c. TRPM8
d. Kir
e. NaV 1.7
Type: multiple choice question
Title: Chapter 05 - Question 39
39. Genetic mutations affecting this channel can cause persistent burning pain sensations?
Feedback: Subhead: Other Channels
Learning Objective: Explain what channelopathies are and provide three examples.
Bloom’s Level: 1. Remembering
a. TRPV1
b. KV 7.1
c. KV 7.2 and KV 7.3
d. KV 7.4
e. NaV 1.7
Type: multiple choice question
Title: Chapter 05 - Question 40
40. Mutations of which gene in cochlear hair cells causes congenital deafness?
Feedback: Subhead: Other Channels
Learning Objective: Explain what channelopathies are and provide three examples.
Bloom’s Level: 4. Analyzing
a. TMC1
b. TMC2
c. KCNQ4
d. TMHS
e. TMIE
Type: multiple choice question
Title: Chapter 05 - Question 41
41. Replacing a codon for one amino acid with another one prior to translation is an example of
Feedback: Subhead: Diversity of Subunits
Learning Objective: Name two mechanism that account for the wide diversity of subunit isotypes found in ion channels.
Bloom’s Level: 2. Understanding
a. gene transcription.
b. glycosylation.
c. RNA editing.
d. alternative splicing.
e. post-translational modification.
Type: multiple choice question
Title: Chapter 05 - Question 42
42. With regard to ion channel opening, the M1 ligand-binding domain of Cys-loop receptors functionally corresponds to which of the following regions of voltage-activated ion channels?
Feedback: Subhead: Conclusion
Learning Objective: Describe the three essential domains that characterize both Cys-loop receptors and voltage-activated channels.
Bloom’s Level: 4. Analyzing
a. S1 transmembrane domain
b. S1-S4 in its entirety
c. S4 transmembrane domain
d. S5-S6, which form the P-loop
e. S6 transmembrane uniquely
Type: multiple choice question
Title: Chapter 05 - Question 43
43. Ion selectivity of Cys-loop and voltage-activated ion channels depends
Feedback: Subhead: Conclusion
Learning Objective: Describe the three essential domains that characterize both Cys-loop receptors and voltage-activated channels.
Bloom’s Level: 2. Understanding
a. inversely on the number of subunits (i.e., fewer subunits means higher ion specificity).
b. directly on the number of subunits (i.e., more subunits means higher ion specificity).
c. on properly spaced charged amino acids in the primary structure of the channel proteins.
d. on auxiliary subunits (e.g., β-subunits), which associate with the main (α) subunit of the channel.
e. on the P-loop.
Type: essay/short answer question
Title: Chapter 05 - Question 44
44. Describe three experimental observations that led to our current understanding of conformational changes of Cys-loop receptors that allow current to flow.
Feedback: First, plunge freezing demonstrated that structural rearrangements of ligand-bound subunits caused larger corresponding movements in the β and γ subunits, compared to δ-subunits, which moved the least. Second, the X-ray structure of a family of bacterial ligand-gated channels, analogous in structure to Cys-loop receptors, showed that channel constriction is relieved via outward displacement of the M2 transmembrane domain. Third, expression M2 peptides in lipid bilayers, in the absence of other portions of the receptor, demonstrated channel conductance and mean open time like the native receptor, which suggests spontaneous fluctuations within the channel structure itself govern opening and open probability, which may pertain to the region of the hydrophobic rings or at the constricted cytoplasmic end of the pore.
Subhead: A Receptor Superfamily.
Learning Objective: Explain the role of the M2 helices in the gating of Cys-loop receptors.
Bloom’s Level: 5. Evaluating
Type: essay/short answer question
Title: Chapter 05 - Question 45
45. Explain the key role of natural high-affinity toxins in discovering and cloning nAChRs and voltage-activated sodium channels? Name the toxins and their targets as a part of your answer.
Feedback: α-bungarotoxin is a highly selective nicotinic receptor antagonist, which was used to separate nAChRs from other membrane proteins after extraction from electrocyte membranes of the electric eel Torpedo. Similarly, tetrodotoxin (TTX) and saxitoxin (STX) were used to separate voltage-activated sodium channels from other membrane proteins after extraction from the electric eel Electrophorus Electricus. In both cases, the essential steps include biochemical extraction and purification of the protein, followed by isolation of cDNA clones, and then deduction of the amino acid sequence.
Subhead: Voltage-Activated Channels.
Learning Objective: Name three types of voltage-activated channels and describe their functional properties.
Bloom’s Level: 2. Understanding
Type: essay/short answer question
Title: Chapter 05 - Question 46
46. Evaluate the evidence that S4 transmembrane domain of voltage-activated sodium channels moves tangent to the plane of the membrane in response to depolarization.
Feedback: When amino acids at either end of the S4 helix were mutated to cysteine via site-directed mutagenesis, sulfhydryl groups on those cysteine residues could be reacted with hydrophilic reagents. Those residues that were inaccessible from outside the cell at rest became accessible when the membrane was depolarized. Likewise, those residues accessible from the inside at the rest state became inaccessible upon depolarization. Those cysteine accessibility experiments strongly suggest S4 translated from inner to outer position within the membrane in response to depolarization.
Subhead: Voltage-Activated Channels
Learning Objective: Name three types of voltage-activated channels and describe their functional properties.
Bloom’s Level: 3. Applying
Type: essay/short answer question
Title: Chapter 05 - Question 47
47. Explain the key role played by blocking molecules in discovering the role of the P-loop in voltage-activated ion channels. Given blocking molecule names as part of your answer.
Feedback: In the region linking S5 and S6 of the voltage-activated sodium channel, point mutations reduced sensitivity to the blocking molecules tetrodotoxin (TTX) and saxitoxin (STX). Furthermore, those point mutations reduced conductance of the channel. Regarding voltage-activated potassium channels, point mutations in the S5-S6 linker region of the Shaker channel reduced its affinity for the blocking molecule tetraethylammonium (TEA) and likewise reduced channel conductance. The most logical explanation is that the linker region of S5-S6 descends back into the membrane and helps form the cytoplasmic-side entry of the channel and its external pore region.
Subhead: Voltage-Activated Channels
Learning Objective: Name three types of voltage-activated channels and describe their functional properties.
Bloom’s Level: 4. Analyzing
Type: essay/short answer question
Title: Chapter 05 - Question 48
48. Create a viable explanation for how calcium activated potassium channels can coexist, and even function cooperatively with voltage-activated calcium channels
Feedback: Voltage-activated calcium channels open during depolarization of the cell membrane. That causes intracellular accumulation of calcium, which is the proximal stimulus that activates (i.e., gates or opens) calcium-activated potassium channels. The calcium-activated potassium channels in turn mediated outward currents that hyperpolarize the cell membrane potential and tend to return the cell to its resting or baseline level of voltage.
Subhead: Voltage-Activated Channels
Learning Objective: Name three types of voltage-activated channels and describe their functional properties.
Bloom’s Level: 5. Evaluating
Type: essay/short answer question
Title: Chapter 05 - Question 49
49. Explain how α and β units differ in their structure and function for voltage-activated sodium channels versus nAChRs?
Feedback: The subunit effectively forms the entire voltage-activated sodium channel, including all of its transmembrane domains, poor-forming region, and its voltage sensor that gates (opens) the channel. By contrast the submit forms just one-fifth of the nAChR (even in a homo-pentameric channel made of 5 α-subunits, any single α-subunit forms one-fifth of the receptor). The α-subunit of the nAChR binds the ligand for nAChRs, but the α-subunit of voltage-activated channels has no equivalent ligand-binding role. β-subunits also make up one-fifth of the nAChR; they occupy nearly the same size as α-subunits and play a similar role in the channel apart from ligand-binding β-subunits in voltage-activated sodium channels are much smaller than the subunit and play an auxiliary role.
Subhead: Voltage-Activated Channels
Learning Objective: Describe the physical structure of a voltage-activated channel.
Bloom’s Level: 5. Evaluating
Type: essay/short answer question
Title: Chapter 05 - Question 50
50. Describe the conceptually different functional roles for Piezo 1 and Piezo 2 in sensory function?
Feedback: Piezo 1 channels are tasked with detecting pressure changes inside the body, pertaining to heart rate, blood flow, distention of internal organs, and sensory modalities generally considered interoception. Piezo 2 channels in contrast are tasked with detecting tissue pressures occurring on the outside of the body, predominantly distention of the skin, which is transduced by primary sensory neurons of the dorsal root ganglia.
Subhead: Mechanoreceptor Channels
Learning Objective: Name two types of mechanoreceptor channels.
Bloom’s Level: 3. Applying
Type: essay/short answer question
Title: Chapter 05 - Question 51
51. Make an argument that TMC in cochlear hair cells is an ion channel.
Feedback: Examining the amino acid sequence of TMC1 on the basis of hydrophobicity suggests that it possesses six membrane-spanning domains with intracellular amino and carboxy terminals. Having six such transmembrane domains as well as cytoplasmic N and C terminals resembles voltage-activated sodium and calcium channels. Moreover, knockout of TMC1 causes deafness, which is evidence of its central role in auditory sensory function, not proving that it is a channel per se, but is consistent with its central importance as expected for a channel.
Subhead: Mechanoreceptor Channels
Learning Objective: Name two types of mechanoreceptor channels.
Bloom’s Level: 5. Evaluating
Type: essay/short answer question
Title: Chapter 05 - Question 52
52. Make an argument for why foods like red peppers are perceived as hot to our sense of taste.
Feedback: TRPV1 channels detect heat, i.e., their gating is temperature dependent. Therefore, neural activity that returns to the brain from nerve fibers that express TRPV1 channels communicates “hot” or “heat” to the brain and is perceived as such. Capsaicin is a naturally occurring chemical found in foods like peppers. Even though food made from peppers may be served at room temperature or slightly elevated temperatures, it nonetheless activates TRPV1-expressing nerve endings and the activity that returns to the brain is thus perceived as heat. Foods that contain pepper-based sauces can even cause individuals to sweat, a heat-related natural response.
Subhead: Other Channels
Learning Objective: Name four different types of stimuli to which transient receptor potential (TRP) channels respond.
Bloom’s Level: 4. Analyzing
Type: essay/short answer question
Title: Chapter 05 - Question 53
53. Make an argument for how the W897X mutation of NaV 1.7 (Scn9a) ion channels leads to “painless” persons who show no ability to perceive pain.
Feedback: The W897X mutation to NaV 1.7 (Scn9a) can be studied by transfecting cDNA for wild-type and mutated channels into human embryonic kidney cells, which express the channels and enable voltage-clamp studies of their currents. The W897X mutant channels pass little to no sodium current in response to conventional depolarizing stimuli. That suggests that in their natural state of being expressed in the skin and its peripheral nervous system, those mutant channels will not pass the inward currents that signify painful stimuli in the limbs or body, and thus the tissue damage (pain-related information) will never be recognized in the central nervous system, thus no sensation of pain for the individual with mutant NaV 1.7 channels.
Subhead: Other Channels
Learning Objective: Explain what channelopathies are and provide three examples.
Bloom’s Level: 4. Analyzing
Type: essay/short answer question
Title: Chapter 05 - Question 54
54. How do gain of function mutations to Scn9a (NaV 1.7) lead to hyperalgesia (excessive or spurious pain)?
Feedback: Gain of function mutations to NaV 1.7 (Scn9a) will pass more inward sodium current in response to conventional depolarizing stimuli. The name “gain of function” implies more function, that is more current than normally expected. That implies that in their natural state of being expressed in the skin and its peripheral nervous system, those gain-of-function mutant channels will pass more inward currents and thus innocuous stimuli would generate activity levels typically associated with tissue damage (pain-related information). The peripheral nervous system, thus mischaracterizing non-damaging stimuli as tissue-damaging would be interpreted as pain by the central nervous system for people with gain-of-function mutant NaV 1.7 channels.
Subhead: Other Channels
Learning Objective: Explain what channelopathies are and provide three examples.
Bloom’s Level: 4. Analyzing
Type: essay/short answer question
Title: Chapter 05 - Question 55
55. Explain the role of KV 7.1 in normal cardiac electrophysiology and cardiac function as well as how mutant KV 7.1 channels with diminished function lead to pathology.
Feedback: KV 7.1 channels function as cardiac delayed rectifiers, which repolarize cardiac action potentials. That function is analogous to the role of neuronal delayed rectifier potassium current in neurons or squid axons. Cardiac action potentials are more long-lasting that neuronal action potentials. In normal cardiac function, the repolarization of the cardiac action potential is a significant part of the cardiac cycle. Thus, when KV 7.1 channels are mutated and function less, then the cardiac action potential lengthens, the cardiac cycle slows and that is recognized as a prolongation from the QRS complex to the T-wave in the electrocardiogram. So-called “Long-QT syndrome” results and that can lead to cardiac pathologies such as fibrillation in the worst-case scenario.
Subhead: Other Channels
Learning Objective: Explain what channelopathies are and provide three examples.
Bloom’s Level: 5. Evaluating
Type: essay/short answer question
Title: Chapter 05 - Question 56
56. If we consider Cys-loop and voltage-activated channels as having three main parts: (1) an extracellular portion, (2) an intramembranous portion, and (3) an intracellular portion; then, provide a general functional attribute for each region and how it functions in both Cys-loop and voltage-activated channels.
Feedback: The extracellular portion of Cys-loop and voltage-activated channels forms the widest portion of the structure. For nAChRs and Cys-loop receptors in general it is a vestibule. that has some role in ion selectivity and forming the mouth of the pore. For all Cys-loop receptors the extracellular portion binds the ligand that gates (opens) the channel. The intramembranous portion forms the ion-selectivity filter and pore. The intramembranous portion forms the gating complex for all voltage-activated channels, that is, it senses membrane voltage and translates that stimulus into structural rearrangement that opens the channel. The intracellular portion affects ion selectivity for Cys-loop receptors, particularly the charge of residues at the intracellular margin of the channel. For voltage-activated channels, the intracellular portion can inactivate the channel by plugging it from the inside. Magnesium ions play a similar role in inwardly rectifying potassium channels even though the magnesium ion is not a structural feature of the channel per se.
Subhead: Conclusion
Learning Objective: Describe the three essential domains that characterize both Cys-loop receptors and voltage-activated channels.
Bloom’s Level: 4. Analyzing
Type: essay/short answer question
Title: Chapter 05 - Question 57
57. Explain how -helices and β-sheets contribute to the specific tertiary and quaternary structural features of Cys-loop receptors like nAChR?
Feedback: -helices form the transmembrane domains M1-M4 as well as the MA cytoplasmic linking M3 and M4. β-sheets form extracellular loops that form the outer vestibule of the receptor.
Subhead: Conclusion
Learning Objective: Describe the three essential domains that characterize both Cys-loop receptors and voltage-activated channels.
Bloom’s Level: 5. Evaluating
Type: essay/short answer question
Title: Chapter 05 - Question 58
58. Evaluate the notion that hydrophilic amino acids line the pore region of Cys-Loop receptors.
Feedback: Using site-directed mutagenesis to replace serine (S) at position 6’ in the putative pore region with a weakly hydrophobic alanine diminished channel conductance, which suggests that hydrophilicity is associated with pore-lining position and functionality. However, leucine and valine, which are strongly hydrophobic, also occupy key positions within the pore region at positions 9′, 13′, and 16′ as identified by cysteine-scanning experiments. Therefore, the evidence that hydrophilic residues line the poor can best be described as equivocal.
Subhead: Conclusion
Learning Objective: Describe the three essential domains that characterize both Cys-loop receptors and voltage-activated channels
Bloom’s Level: 5. Evaluating