SNAPP Week 2: Concepts and Questions

Question 1

During conduction of an action potential down an axon, what determines outward membrane current?

Answer 1

Pk
.
Pk determines outward membrane current and Pna determines inward membrane current

Question 2

At which point during an action potential is the driving force of sodium ions the smallest?

Answer 2

at peak.

the driving force for Na approaches zero at the peak of an AP because Vm is approaching Ena. The driving force on any ion is always the difference between the membrane potential and that ion’s equilibrium potential.

Question 3

You stimulate an AP in an axon and attempt to stimulate another 1 ms later but you do not get a response. What is happening in sodium channels during the refractory period?

Answer 3

m gates open but h gates remain shut.

m (activation gates) open in response to stimuli but h (inactivation gates) take time to reopen after an action potential.
Refractory periods are caused by the delay in h gates to reopen after depolarization

Absolute = no AP no matter high much stimulus there is Relative = additional stimulus required to produce an AP (this means that some h gates are open but not all of them)
[In some channels, it may be that both m and h gates are shut (choice c)]

Question 4

Increasing resistance (R) of the membrane will have which of the following effects?

Answer 4

increase conduction velocity of an axon

increasing membrane resistance will prevent the flow of ions back across the plasma membrane. Since fewer ions are leaking out, the AP will be stronger and faster than it would be with a lower membrane resistance (this is one of the functions of myelin)

Question 5

You stimulate an axon at two separate points. How many action potentials are generated and what will happen when the two AP’s collide?

Answer 5

4, 2 of which will stop when they collide with each other

4 AP’s generated. When they collide both will stop because adjacent AP’s are in refractory periods.

Question 6

At the peak of an action potential Vm is

Answer 6

positive

positive (approaches ENa)

Question 7

Which of the following is a defining feature of apoptosis?

Answer 7

Collapsed nucleus is the defining morphological feature of apoptosis

Question 8

*In the intrinsic pathway of apoptosis, which protein acts as the “executioner?

Answer 8

Caspase 3

Question 9

*E. coli bacteria induces diarrhea by making an enzyme that affects the extrinsic pathway of apoptosis, what is the function of this enzyme?

Answer 9

It glycosylates FADD and makes in unable to activate caspase 8.

Question 10

Which is not a main type of autophagy

Answer 10

Protease-mediated autophagy.

Macroautophagy, microautophagy, and chaperone-mediated autophagy are the main types

Question 11

Autophagy is induced during times of?

Answer 11

Nutrient Stress

Question 12

Order the following steps of macroautophagy correctly.

Answer 12

The process of macroautophagy is:

1) Activate a PI3K complex that allows nucleation of a membrane that will eventually form the autophagosome.
2) Regulation of protein conjugation events to extend membrane.
3) Randomly capture or specifically deliver cargo to the extending autophagosome, then join the membrane to close the vesicle
4) Fuse with lysosome
5) Recycle amino acids and other macromolecular precursors.

Question 13

As a fourth year medical student you are doing a clinical rotation in Haiti. You see a patient that you suspect has cholera. What initial symptom does the patient report that leads you to think it is cholera?

Answer 13

Voluminous diarrhea.

The most classic clinical symptom of cholera is voluminous (up to 1 liter per hour) watery feces. While it is possible that these other symptoms could happen as a secondary result, they are not the most likely thing to happen with cholera.

Question 14

Which of the following transporters is located on the apical membrane and is the cause of the ionic efflux that leads to severe diarrhea:

Answer 14

CFTR channel

CFTR is a chloride channel on the apical side (affected by cholera and CF). The massive efflux of chloride ions causes water to follow and produces diarrhea.

Question 15

After the cholera toxin binds to the GM1 receptor on the cell’s membrane, what happens next?

Answer 15

The A subunit is cleaved, endocytosed, and cAMP is produced.

There are two subunits to the cholera toxin: A and B. The A is the active site while B is the transport molecule. The whole toxin binds to the GM1 receptor, but only A is cleaved and endocytosed. This in turn activates adenylyl cyclase which produces cAMP. This leads to activation of CFTR which leads to efflux of chloride ions.

Question 16

Which of the following is true regarding antibiotic treatment of cholera:

Answer 16

They can shorten the duration of disease.

Antibiotics can shorten the duration of the disease, but should only be used in severe cases. Antibiotics are not the standard of care (delivery of fluids or oral dehydration therapy is standard). However, when used they will decrease the risk of further infectivity.

Question 17

A patient presents to your clinic requesting medication preparations for cholera. The patient is planning a 2 week mission trip to Haiti where there has been a major cholera outbreak. He has already received ORT supplies for his trip. He will be staying in a small village where he will be preparing meals for the local people as well as volunteers from the Red Cross, and is departing in four days. His family has been doing mission work for many years, and both of his parents have had a history of cholera from when they were living in Bangladesh during the early 1990’s. Besides ORT, what do you recommend to this patient?

Answer 17

Nothing The cholera vaccine is not licensed in the US, and is only effective after the second dose, and doses must be given one week apart. Only recommended for long durations of stay in a place where cholera is endemic (he is only going for 2 weeks) Antibiotics are only used for severe cases Antidiarrheals are never recommended He already has ORT so you don’t need to give him anything Advise on sanitation, handwashing, and careful water and food choices

Question 18

Which of the following is correct regarding the Na/K/Cl exchanger of epithelial cell membranes?

Answer 18

drives the uptake of Cl into the cell that results in NaCl secretion

the Na/K/Cl exchanger is located on the Basolateral membrane It relies on energy from Na leakage to uptake Cl (causes high Cl concentrations) Eventually Cl leaks out into the lumen (apical side) and drags Na and water with it = secretion

Question 19

What is the maximum concentration of urine solutes?

Answer 19

1200 mosM

Question 20

At the beginning of a relative refractory period, the k gates are in which position?

Answer 20

most are open.

most K gates are open at the beginning of a relative refractory period If K gates are open Vm is more negative. Higher K conductance makes it harder to depolarize the membrane to threshold for an AP.

Question 21

A seven year old female patient presents to your clinic with elevated k levels and a venous pH of 7.01. What other symptoms are to be expected in this patient?

Answer 21

nausea, decreased appetite, weight loss

DKA patients are not typically febrile Dry mucosa, cracked lips, sunken eyes/cheeks Weight loss, decreased appetite, vomiting, somnolence Polyuria, polydipsia (diabetes) Delayed capillary refill Fruity breath Increased/rapid respiration ‘Kussmaul’ respirations (trying to excrete CO2)

Question 22

A beta cell in the pancreas receives a signal to close its potassium channels. The cell depolarizes and calcium enters the cell. Which of the following correctly describes the next step in this signaling pathway?

Answer 22

calcium influx triggers the exocytosis of insulin

Question 23

Binding of an agonist to a G-protein coupled receptor at its transmembrane domain causes a conformational change that results in which of the following functions?

Answer 23

activates the receptor and triggers signal transduction to begin

agonists activate GPCR’s and cause a conformational change that begins signal transduction. On the G alpha subunit GDP - GTP by a GEF GTP on G-alpha subunit allows it to go to effectors (enzymes that make 2nd messengers or ion channels that control perm) An intrinsic GTPase returns the GPCR back to its inactive state by hydrolyzing GTP to GDP.

Question 24

When G-protein coupled receptors are active, which components modulate their downstream effectors?

Answer 24

G beta-gamma and G alpha subunits

beta-gamma and alpha(bound to GTP) mediate effector regulation When receptor is in its active state, beta-gamma and free alpha are dissociated from each other and alpha is bound to GTP.

Question 25

During G-protein coupled signaling, binding of GTP to G alpha subunits results in which of the following?

Answer 25

decreased binding affinity of G alpha and beta-gamma subunits hydrolysis of GTP will cause inactivation (GDP binding to alpha) which tells beta-gamma and alpha to re-associate at the GPCR. During activation, GTP causes the affinity of alpha for beta to decrease so that it can increase affinity for its effectors. Bordatella pertussis = locks GCPR in its inactive state (GDP bind) Cholera toxin = locks CFTR in its active state (GTP)

Question 26

Alpha adrenergic receptor activation triggers peripheral vasoconstriction via which of the following second messengers?

Answer 26

IP3 and DAG alpha adrenergic receptors trigger peripheral vasoconstriction of smooth muscle that increases BP at the lungs, heart and skeletal muscle. IP3 and DAG 2nd messengers - Ca into cytosol - smooth muscle contraction ACE-inhibitors decrease BP by inhibiting peripheral vasoconstriction.

Question 27

Atropine is a drug administered to increase heart rate. How does atropine work?

Answer 27

M2 antagonist atropine antagonizes the acetylcholine (Ach)pathway at the m2 muscarinic cholinergic receptor, which normally activates K+ channels to hyperpolarize heart muscle cells and decrease heart rate. Thus, atropine causes increased heart rate by preventing m2 receptor-mediated hyperpolarization. K+ channels are the most direct targets of m2 receptors; L-type Ca2+ channels are more indirect targets through Gi inhibition of adenylyl cyclase-cAMP-PKA signaling.

Question 28

Caffeine acts by:

Answer 28

caffeine inhibits phosphodiesterases (that hydrolyze cAMP to AMP which turns off PKA) Increases PKA levels

Question 29

Which of the following is a true statement regarding ion channels?

Answer 29

Ion channels are seen in the plasma membrane and the membrane of intracellular organelles Ion channels are present in plasma membranes and in the membranes of intracellular organelles. Their gating is controlled by a vast array of stimuli. Some channels respond to multiple stimuli Ion channels are essential for function of diverse cell types, including muscle, neurons, T lymphocytes and pancreatic B cells. Ion channels are important targets of natural products for predation and also therapeutic targets. Mutations of ion channels are responsible for diverse human diseases

Question 30

Channel selectivity of Ion channels can be based on which of the following?

Answer 30

Charge Size Dehydration Multiple Binding Sites Selectivity of channels varies. Some channels are highly selective and some are moderately selective. The charge is very important, cation/anion. Also the valence can matter. Ion size, dehydration and multiple binding sites can also affect selectivity of an ion channel.

Question 31

A Kv and Nav structured ion channel has a unique way of “voltage-sensing”, how is this accomplished?

Answer 31

S4 helices Voltage sensing is accomplished by S4 helices, the helices contain a positively charged Arg or Lys every 3rd position and translocate in response to changes of the S4 helices cause opening of the activation gate.

Question 32

What role to B-cells play in MS

Answer 32

They activate effector T-cells They activate effector T-cells This is why targeting and depleting specific B-cells is an effective therapy in MS

Question 33

Myelin is important for neuron function because it:

Answer 33

Increases resistance Myelin increases resistance (charge cannot diffuse out to repolarize the cell in myelinated regions, effectively making the membrane more resistant to current), allowing for faster conduction of the action potential. Myelin decreases capacitance so there is less charge that is need to produce an AP. Larger axons have increased surface area and increased cross-sectional area, but these properties are not related to myelination.

Question 34

An MRI on a patient shows lesions consistent with MS. You test the patient's visual pathway using a Visually Evoked Potential, and notice a decrease in amplitude but not a delay in response. What is the most likely conclusion you can make at this time?

Answer 34

The patient has lost some neuronal axons Decreased amplitude = loss of axons Decreased speed = demyelination Without additional studies and time, one cannot definitively conclude that this is or is not MS, or that this is autoimmunity This finding is still consistent with MS, later tests will show progression of a longer latent period and decreased amplitude

Question 35

What is the function of K+ channel blockers as a treatment for MS?

Answer 35

K+ channel blockades enhance AP conduction by preventing rapid repolarization via K+ efflux K+ channel blockers prolong action potentials by inhibiting K+ channels that normally allow rapid K+ efflux during repolarization. They do not stop the progression of disease, they just help people walk better (delfampridine) Seizures are a common side effect because AP's in the brain are also prolonged.

Question 36

Which of the following people is at most risk for developing multiple sclerosis (MS)?

Answer 36

A female between 16-45 years. A female between 16-45 80% of patients have onset between 16-45 Females have 2.4 to 1 risk ratio. Exposures and risks are determined during first 15 years of life

Question 37

Neurodegenerative diseases such as Alzheimer’s that result from the accumulation of plaques within the nucleus might be caused by:

Answer 37

a decreased ability of the NPCs to exclude molecules from nuclear entry as you age As you age, NPCs lose their ability to effectively exclude molecules from the nucleus which results in the accumulation of plaques inside the nucleus

Question 38

When is asymmetry of NPC's established?

Answer 38

during the cell cycle Asymmetry of NPC's on the nuclear envelope is established during the cell cycle. Number varies between different cells and species.

Question 39

Which of the following components of nucleoporin structure is highly conserved between species?

Answer 39

three-dimensional architecture 3D structure of nucleoporins is highly conserved. 30% of nups contain FG repeats Nups = nucleoporins, 30 distinct proteins repetitively arranged 8 filaments outside (cytoplasmic), 8 filaments inside that form nuclear basket F compartments repel each other so proteins are natively unfolded without secondary structure or a hydrophobic core (tails to not end up in an aggregated shape)

Question 40

Where in the cell can a high concentration of RAN-GTP be found?

Answer 40

nucleus nucleus because this is where it acts by disassembling cargo molecules from their cargo receptors, or acting as an allosteric modifier for export receptors.

Question 41

Directionality of protein transport is determined by

Answer 41

the RAN cycle the RAN cycle determines protein directionality. Enzyme location determines RAN's GTP bound or unbound state (RanGAP at the cytoplasmic face of the NPC, the exchange factor RCC1 in the nucleus) RAN-GTP is high in the nucleus, low in the cytosol mRNA transport doesn't use RAN (energy consumed by Dbp5, an ATP-dependent RNA helicase tethered to cytoplasmic face of NPC) rRNA transport uses both GTP (Ran) and ATP (Dsb5).

Question 42

*Which of the following is NOT a major protein degradation pathway?

Answer 42

Apoptosis Autophagy,UPS (ubiquitin-proteasome system), Lysosome are.

Question 43

*Which describes the action of Hsp60?

Answer 43

Hsp60 acts by forming an elaborate barrel shaped structure that acts as an isolation chamber to help refold the misfolded protein

Question 44

Major functions of the ER are:

Answer 44

Co-translational folding of proteins. The functions of the ER are: Synthesis of lipids (phospholipids, ceramide, cholesterol—mainly in sER) Control of cholesterol homeostasis (cholesterol sensor and synthesis) Storage of Ca2+ (rapid uptake and release) Synthesis of proteins on membrane bound ribosomes (rough ER) Co-translational folding of proteins and early post translational modifications Quality control. Functions of the golgi are: Synthesis of complex sphingolipids from the ceramide backbone,Adding post-translational modification of proteins and lipids,There are multiple compartments, stacked like pancakes with cis and trans end

Question 45

Which is a major function of the Golgi?

Answer 45

Synthesis of complex sphingolipids from the ceramide backbone Additional post-translational modifications of proteins and lipids Proteolytic processing Sorting of proteins and lipids for post-golgi comprtments

Question 46

*Which of the following is paired correctly regarding coat structures and their function?

Answer 46

COPII: ER to golgi: forward COPI: golgi to ER: backward Clathrin: golgi to plasma membrane