Which of the following statements about diffusion is FALSE?

• a.
  

  Molecules diffuse from regions of high concentration to regions of low concentration.

  
  
• b.
  

  Diffusion flux ( J ) is directly proportional to the concentration gradient (Δ C/ Δ x ).

  
  
• c.
  

  Diffusion tends to even out concentration differences.

  
  
• d.
  

  Diffusion is the result of the random motion of molecules.

  
  
• e.
  

  The distance molecules diffuse is directly proportional to time (i.e., d ∝ t ).

If a collection of molecules is found to diffuse a distance d in 9 seconds, how long will it take the same molecules to diffuse twice as far?

• a.
  

  9 seconds.

  
  
• b.
  

  18 seconds.

  
  
• c.
  

  36 seconds.

  
  
• d.
  

  81 seconds.

  
  
• e.
  

  None of the above.

Which of the following statements about membrane permeability is FALSE?

• a.
  

  The cell membrane is more permeable to small, nonpolar solutes than to polar solutes because nonpolar solutes dissolve better in the membrane.

  
  
• b.
  

  A difference in solute concentration on the two sides of the membrane can drive a diffusive flux of molecules through the membrane.

  
  
• c.
  

  Increasing the thickness of a membrane reduces the diffusive flux through the membrane.

  
  
• d.
  

  The net solute flux through a cell membrane is the result of balancing influx and efflux.

  
  
• e.
  

  Increasing the diffusion coefficient of a solute molecule in the membrane does not change the permeability of the membrane to that solute.

If the extracellular and intracellular Na ⁺ and K ⁺ concentrations are symbolized as [Na ⁺ ] _o , [Na ⁺ ] _i , [K ⁺ ] _o , and [K ⁺ ] _i , and the respective membrane permeabilities are symbolized as P _Na and P _K , which of the following statements about unidirectional fluxes in a resting cell is incorrect?

• a.
  

  J _Na,out→in = P _Na [Na ⁺ ] _o

  
  
• b.
  

  J _K,in→out = P _K [K ⁺ ] _i

  
  
• c.
  

  J _Na,out→in > J _Na,in→out

  
  
• d.
  

  J _Na,out→in > J _K,in→out

  
  
• e.
  

  J _K,in→out > J _K,out→in

A cell containing 300 mM nonpermeant solute is initially equilibrated with an extremely large volume of plasma that also contains 300 mM nonpermeant solute. The initial cell volume is 1 picoliter. The solute concentration of the plasma is then suddenly increased by the addition of 100 mM of a permeant solute. Which of the following is FALSE?

• a.
  

  After new osmotic equilibrium is reached, the cell volume will be 1 picoliter.

  
  
• b.
  

  The final concentration of permeant solute in the cell will be 100 mM.

  
  
• c.
  

  After new osmotic equilibrium is reached, the cell volume will be 0.75 picoliter.

  
  
• d.
  

  The final concentration of nonpermeant solute inside the cell will be 300 mM.

  
  
• e.
  

  The cell will initially shrink slightly and then recover to its original volume.

Which of the following statements is FALSE?

• a.
  

  Injecting, into the circulation, a substance that cannot cross the blood-brain barrier tends to reduce brain edema.

  
  
• b.
  

  Adding a permeant solute to the plasma will cause red blood cells to shrink permanently.

  
  
• c.
  

  Inflammatory mediators released by mast cells increase the permeability of capillary walls, thus leading to edema.

  
  
• d.
  

  Capillary hydrostatic pressure drives fluid filtration, whereas capillary colloid osmotic pressure drives fluid reabsorption.

  
  
• e.
  

  Proteins that cannot readily permeate the capillary wall are the principal cause of the osmotic pressure difference between the plasma and the interstitial tissue fluid.

The membrane potential of a cell is V _m = –60 mV, and the intracellular and extracellular Cl ⁻ concentrations are [Cl ⁻ ] _i = 7 mM and [Cl ⁻ ] _o = 105 mM, respectively. Which of the following statements is FALSE? (Note: At 37°C, RT / F = 26.7 mV and 2.303 RT / F = 61.5 mV)

• a.
  

  The Cl ⁻ current is inward.

  
  
• b.
  

  The Cl ⁻ flux is inward.

  
  
• c.
  

  The Cl ⁻ equilibrium potential is E _Cl = –72 mV.

  
  
• d.
  

  There is an outward driving force on Cl ⁻ .

  
  
• e.
  

  If V _m = E _Cl , there will be no net flux of Cl ⁻ ions across the cell membrane.

Which of the following is (are) essential for generating a stable, nonzero membrane potential?

• a.
  

  The cell membrane must be permeable to at least one type of ion.

  
  
• b.
  

  The net current through the plasma membrane must be zero.

  
  
• c.
  

  The net flux of ions through the plasma membrane must be zero.

  
  
• d.
  

  a and b are correct.

  
  
• e.
  

  a, b, and c are correct.

If the cell’s Na ⁺ pumps are inhibited by ouabain, all of the following will happen EXCEPT:

• a.
  

  The Donnan effect will cause osmotic imbalance.

  
  
• b.
  

  [K ⁺ ] will fall in the cell.

  
  
• c.
  

  The membrane potential will hyperpolarize.

  
  
• d.
  

  The cell volume will increase.

  
  
• e.
  

  [Na ⁺ ] will rise in the cell.

For a neuron, the equilibrium potentials for several common ions were found to be E _H = –12 mV, E _Na = +50 mV, E _K = –90 mV, E _Ca = +135 mV, and E _Cl = –50 mV. If the membrane potential of the neuron is at V _m = –60 mV, which of the following statements about ion fluxes is FALSE?

• a.
  

  Cl ⁻ flux is inward and H ⁺ flux is inward.

  
  
• b.
  

  The K ⁺ and Na ⁺ fluxes flow in opposite directions.

  
  
• c.
  

  Ca ²⁺ flux is inward and Na ⁺ flux is inward.

  
  
• d.
  

  There is net H ⁺ influx, which would tend to make the inside of the cell more acidic.

  
  
• e.
  

  If more Cl ⁻ channels are opened, the resulting change in Cl ⁻ flux will tend to depolarize the cell.

Intracellular and extracellular concentrations for the three common monovalent ions are given here for a cell.

• 
  

  If the relative permeabilities for the three ions are 1:10:0.2 (K ⁺ :Na ⁺ :Cl ⁻ ), what is the expected V _m of the cell (rounding to two significant digits)? ( Note: At 37ºC, RT / F = 26.7 mV and 2.303 RT / F = 61.5 mV.)

  
  
• a.
  

  –89 mV.

  
  
• b.
  

  –53 mV.

  
  
• c.
  

  –33 mV.

  
  
• d.
  

  +52 mV.

  
  
• e.
  

  +90 mV.

Which of the following statements is FALSE?

• a.
  

  Chemical potential energy is stored in concentration gradients.

  
  
• b.
  

  The electrochemical potential for an ion is zero if the membrane potential is at V _m = 0 mV.

  
  
• c.
  

  If the electrochemical potential of an ion is the same on the inside and outside of the cell membrane, that ion is at equilibrium.

  
  
• d.
  

  Diffusion is an example of a transport process driven by a gradient in electrochemical potential.

  
  
• e.
  

  A gradient in electrochemical potential drives the passive transport of ionic substances.

After demyelination, the axonal membrane in the region between two nodes of Ranvier:

• a.
  

  Depolarizes at approximately the same rate during a propagated action potential as it did before demyelination.

  
  
• b.
  

  Has a smaller membrane time constant (τ _m ) because the membrane resistance is lower and the membrane capacitance is unchanged.

  
  
• c.
  

  Has a lower membrane resistance and more charge separation across the membrane at the resting potential.

  
  
• d.
  

  Has a larger membrane time constant (τ _m ) because the membrane capacitance is larger and the membrane resistance is unchanged.

  
  
• e.
  

  None of the above.

Two nonmyelinated axons have the same resistance and capacitance per unit area of membrane but are different in diameter. The passive cable properties of these axons were investigated, and the following values of resistance and capacitance per unit length of axon were determined (assume that r _o = 0):

• 
  

  Which of the following is TRUE?

  
  
• a.
  

  The membrane time constant in axon 1 is smaller than in axon 2.

  
  
• b.
  

  Axon 2 is larger in diameter than axon 1.

  
  
• c.
  

  The effect of a subthreshold stimulus can be seen over a longer distance in axon 2 than in axon 1.

  
  
• d.
  

  The action potential would propagate faster in axon 1.

  
  
• e.
  

  The length constant is the same in both axons.

All of the following contribute to the muscle paralysis found in hyperkalemic periodic paralysis EXCEPT:

• a.
  

  Some Na ⁺ channels are open in the steady state, thus causing membrane depolarization.

  
  
• b.
  

  Some Na ⁺ channels do not inactivate completely.

  
  
• c.
  

  An increase in extracellular K ⁺ produces membrane depolarization.

  
  
• d.
  

  Membrane depolarization increases Na ⁺ efflux through the Na ⁺ pump and results in a reduction in the amount of Ca ²⁺ stored in the sarcoplasmic reticulum.

  
  
• e.
  

  Membrane depolarization causes skeletal muscle to become mechanically inactivated.

All of the following are true of voltage-gated L-type Ca ²⁺ channels EXCEPT:

• a.
  

  Their open probability increases as V _m moves in the positive direction.

  
  
• b.
  

  They can be opened by phosphorylation.

  
  
• c.
  

  During an action potential generated by voltage-gated Ca ²⁺ channels, the amount of Ca ²⁺ entering the cell can significantly increase [Ca ²⁺ ] _i .

  
  
• d.
  

  The number of activatable Ca ²⁺ channels in cardiac cell membranes can be altered by increasing the concentration of intracellular cAMP.

  
  
• e.
  

  They are blocked by dihydropyridines (e.g., nifedipine).

Which of the following statements about current flow across an “isolated patch” of membrane (e.g., a small spherical cell) is FALSE?

• a.
  

  An inward ionic current will produce a depolarization only if it causes an outward capacitive current.

  
  
• b.
  

  Outward capacitive current always causes V _m to become more positive.

  
  
• c.
  

  Inward capacitive current never causes V _m to become more positive.

  
  
• d.
  

  An outward ionic current can never cause V _m to become more positive.

  
  
• e.
  

  While current is being passed across the membrane through an external current source, the capacitive current is equal in magnitude, and opposite in direction, to the ionic current.

Assume that a Na ⁺ channel stays open and allows Na ⁺ ions to flow through at all times. Which of the following statements about the current through this single open Na ⁺ channel is FALSE?

• a.
  

  The current has a constant amplitude if the membrane potential is held at a constant level.

  
  
• b.
  

  The current would decrease in amplitude as V _m changed from the resting potential to the peak of the action potential.

  
  
• c.
  

  The current would increase and then decrease while V _m was voltage clamped at 0 mV.

  
  
• d.
  

  The current amplitude can be calculated from Ohm’s Law.

  
  
• e.
  

  The net current through the channel is zero if V _m is at E _Na .

Which of the following would be the Cl ⁻ current flowing through 100 open Cl ⁻ channels if V _m is –70 mV, E _Cl is –45 mV, and the conductance of a single open chloride channel is 20 pS (pS = 10 ⁻¹² S; 1 S = 1 A/V).

• a.
  

  50 pA.

  
  
• b.
  

  –50 pA.

  
  
• c.
  

  0.5 pA.

  
  
• d.
  

  –0.5 pA.

  
  
• e.
  

  –250 pA.

Which of the following statements about BK _Ca channels is FALSE?

• a.
  

  In neurons that generate a burst of action potentials, outward current through BK _Ca channels helps terminate the burst.

  
  
• b.
  

  BK _Ca channels could contribute outward current to help repolarize individual action potentials.

  
  
• c.
  

  BK _Ca channels always carry outward current under physiological conditions.

  
  
• d.
  

  At V _m = –80 mV, and [Ca ²⁺ ] _i <100 nM, BK _Ca channels are mostly closed.

  
  
• e.
  

  Ca ²⁺ ions bind to a site on the extracellular side of the BK _Ca channel to activate the channel.

When the plasma glucose concentration rises to more than approximately 5 mM, pancreatic β-cells secrete insulin in response to a rise in [Ca ²⁺ ] _i . [Ca ²⁺ ] _i increases because:

• a.
  

  Glucose blocks K _ATP channels, thus leading to membrane depolarization and the opening of voltage-gated Ca ²⁺ channels.

  
  
• b.
  

  Glucose binds to a receptor on the voltage-gated Ca ²⁺ channel and increases the channel open probability.

  
  
• c.
  

  Glucose metabolism increases [ATP] _i and ATP directly opens voltage-gated Ca ²⁺ channels.

  
  
• d.
  

  Glucose metabolism increases [ATP] _i and ATP blocks K _ATP channels, thus leading to membrane depolarization and the opening of voltage-gated Ca ²⁺ channels.

  
  
• e.
  

  None of the above.

All of the following events are involved in the increase in cardiac contractility caused by epinephrine EXCEPT:

• a.
  

  The cytosolic cAMP concentration increases.

  
  
• b.
  

  Ca ²⁺ entry through voltage-gated L-type Ca ²⁺ channels is enhanced.

  
  
• c.
  

  Na/Ca exchangers in the plasma membrane are inhibited.

  
  
• d.
  

  cAMP-dependent protein kinase phosphorylates L-type Ca ²⁺ channels.

  
  
• e.
  

  Epinephrine activates adenylyl cyclase by binding to β-adrenergic receptors.

Which of the following statements is FALSE?

• a.
  

  Voltage-gated K ⁺ channels in squid axons and A-type K ⁺ channels are opened by membrane depolarization, but the open probability of Ca ²⁺ -activated K ⁺ channels decreases with depolarization.

  
  
• b.
  

  Under physiological conditions a current flowing through any type of K ⁺ channel tends to oppose membrane depolarization.

  
  
• c.
  

  A-type K ⁺ channels inactivate during maintained depolarization.

  
  
• d.
  

  Ca ²⁺ -activated K ⁺ channels can be opened by an increase in [Ca ²⁺ ] _i .

  
  
• e.
  

  All K ⁺ channels normally pass outward current under physiological conditions.

Which of the following statements concerning the voltage-gated macroscopic Na ⁺ ( g _Na ) and K ⁺ ( g _K ) conductances of the squid giant axon is FALSE?

• a.
  

  In a voltage clamp experiment, if the V _m is stepped to 0 mV, g _Na would activate faster than g _K .

  
  
• b.
  

  Both g _Na and g _K are voltage-dependent and time-dependent.

  
  
• c.
  

  Both g _Na and g _K have an activation and an inactivation phase during a depolarizing voltage clamp step.

  
  
• d.
  

  g _Na is proportional to the number of open Na ⁺ channels.

  
  
• e.
  

  g _K is proportional to the probability that a K ⁺ channel is open.

Which of the following events does NOT occur during a propagated action potential along a myelinated nerve axon?

• a.
  

  Propagation occurs by local circuit current flow.

  
  
• b.
  

  Inward Na ⁺ current at one node of Ranvier causes inward current to flow at an adjacent node, which depolarizes that node toward threshold.

  
  
• c.
  

  Na ⁺ channels become inactivated.

  
  
• d.
  

  The action potential rapidly propagates from one node of Ranvier to the next.

  
  
• e.
  

  If E _Cl is always more negative than the V _m , an outward Cl ⁻ current is flowing.

All of the following statements are true of membrane capacitance ( C _m ) EXCEPT:

• a.
  

  The decrease in C _m that results from demyelination is one of the factors contributing to slowing or blocking of action potential propagation.

  
  
• b.
  

  Biological membranes typically have a C _m of approximately 1 × 10 ⁻⁶ F/cm ² .

  
  
• c.
  

  The rate of change of V _m in a small spherical cell, in response to a constant current stimulus, would decrease if C _m increased while R _m did not change.

  
  
• d.
  

  C _m is equal to the amount of charge separated across the membrane, in coulombs, per volt of membrane potential.

  
  
• e.
  

  If the V _m is changing, the amount of charge separated across the membrane is changing and a capacitive current is flowing.

All of the following statements about voltage-gated Na ⁺ channels are true EXCEPT:

• a.
  

  They pass only inward current under normal physiological conditions.

  
  
• b.
  

  K ⁺ ions interfere with Na ⁺ channel inactivation in skeletal muscle cells from patients with hyperkalemic periodic paralysis.

  
  
• c.
  

  They have an open probability that depends on time and V _m .

  
  
• d.
  

  They inactivate during the action potential, causing the membrane to be refractory to additional stimuli for a short period of time.

  
  
• e.
  

  Inward current through Na ⁺ channels in axons generates the upstroke of the action potential.

Which of the following is NOT a property of all ion channels?

• a.
  

  Ion channels increase the permeability of the membrane to ions.

  
  
• b.
  

  Ion channels are integral membrane proteins that extend across the lipid bilayer.

  
  
• c.
  

  An ion channel is a pore that is not open at all times.

  
  
• d.
  

  Ion channels exhibit selectivity by allowing only certain ions to flow through the channel.

  
  
• e.
  

  All of the above are properties of all ion channels.

Which of the following statements about ion channel structure is FALSE?

• a.
  

  Voltage-gated Na ⁺ , K ⁺ , and Ca ²⁺ channels contain structural similarities indicating that they are members of a gene superfamily.

  
  
• b.
  

  Voltage-gated Na ⁺ , K ⁺ , and Ca ²⁺ channels contain a P region, or loop, that lines the pore of the channel.

  
  
• c.
  

  Inward-rectifier K ⁺ channels and voltage-gated K ⁺ channels are composed of subunits with six membrane-spanning helical segments.

  
  
• d.
  

  The selectivity filter in the bacterial KcsA K ⁺ channel is formed by several main-chain carbonyl oxygen atoms from amino acids in the P region.

  
  
• e.
  

  Voltage-gated Na ⁺ , K ⁺ , and Ca ²⁺ channels all contain a membrane-spanning segment (S4) having several positive charges that act as a voltage sensor.

All of the following are true of membrane transport EXCEPT:

• a.
  

  Aquaporins are responsible for high water permeability across some cell membranes.

  
  
• b.
  

  Single carrier molecules, such as the simple glucose carrier (GLUT), can transport substrate at a rate of 1000 to 5000 molecules/second.

  
  
• c.
  

  Insulin modulates the glucose carriers (GLUTs) in skeletal muscle and thereby speeds the rate of glucose uptake into these cells, but it does not affect the intracellular glucose concentration in the cells under steady-state conditions.

  
  
• d.
  

  The diffusion of nonpolar compounds across cell membranes is directly proportional to their solubility in water.

  
  
• e.
  

  Ions normally cross the plasma membrane at a very slow rate unless they are transported by special integral membrane proteins (e.g., carriers, channels, or pumps).

All of the following are characteristic of transport across cell membranes EXCEPT:

• a.
  

  Carriers behave like channels that are open to only one side of the membrane at a time.

  
  
• b.
  

  Carriers that mediate facilitated diffusion of a single solute species cannot maintain a concentration gradient for that solute in the steady state.

  
  
• c.
  

  Carriers that mediate facilitated diffusion of a single solute species can “cycle” only when the solute is bound.

  
  
• d.
  

  Carrier-mediated transport can be modulated by phosphorylation.

  
  
• e.
  

  Carrier-mediated transport can be regulated by cycling carriers into and out of the plasma membrane.

Glucose absorption in the intestinal tract and reabsorption in the renal tubules are dependent on Na ⁺ -glucose cotransporters (SGLTs) in the brush border membranes of intestinal and renal epithelial cells. Assume that:

• 
  

  The glucose concentration in the blood plasma = 4 mM.

  
  
• 
  

  The Na ⁺ concentrations are 145 mM in blood plasma, 10 mM in the cytoplasm, and 135 mM in kidney tubular fluid.

  
  
• 
  

  V _m is –62 mV (cytosol with respect to tubule lumen) and –58 mV (cytosol with respect to blood plasma).

  
  
• 
  

  RT / F = 26.7 mV.

  
  
• 
  

  What is the theoretical limit to which an Na ⁺ -glucose cotransporter, with a 1 Na ⁺ :1 glucose coupling ratio (SGLT-2), could reduce the glucose concentration in the tubule lumen?

  
  
• a.
  

  0.4 mM.

  
  
• b.
  

  0.3 mM.

  
  
• c.
  

  0.2 mM.

  
  
• d.
  

  0.04 mM.

  
  
• e.
  

  0.03 mM.

All of the following are true of glucose transport in human cells EXCEPT:

• a.
  

  All cells express Na ⁺ -glucose cotransporters (SGLT).

  
  
• b.
  

  Some cells express Na ⁺ -glucose cotransporters with a coupling ratio of 1 Na ⁺ :1 glucose.

  
  
• c.
  

  Some cells express Na ⁺ -glucose cotransporters with a coupling ratio of 2 Na ⁺ :1 glucose.

  
  
• d.
  

  All cells that express Na ⁺ -glucose cotransporters (SGLT) must also express (simple) glucose carriers (GLUT).

  
  
• e.
  

  The simple glucose carrier (GLUT) activity in some cell types is modulated by insulin.

The Na ⁺ /Ca ²⁺ exchanger in vertebrate photoreceptors (rod and cone cells in the retina) mediates the exchange of 4 Na ⁺ for 1 Ca ²⁺ plus 1 K ⁺ . A rise in the extracellular K ⁺ concentration can be expected to:

• a.
  

  Decrease the exchanger-mediated transport of Ca ²⁺ from the cytoplasm to the extracellular fluid.

  
  
• b.
  

  Increase the exchanger-mediated transport of Ca ²⁺ from the cytoplasm to the extracellular fluid because of a reduction in the K ⁺ concentration gradient.

  
  
• c.
  

  Increase the exchanger-mediated transport of Ca ²⁺ from the cytoplasm to the extracellular fluid because of a membrane depolarization.

  
  
• d.
  

  Increase the exchanger-mediated entry of Na ⁺ into the cells.

  
  
• e.
  

  b, c, and d are all correct.

The following are all characteristics of Na ⁺ pumps EXCEPT:

• a.
  

  Na ⁺ pumps in the kidney and in the brain consume more than half of the ATP hydrolyzed in those organs.

  
  
• b.
  

  The hormone aldosterone regulates Na ⁺ pumps by promoting the synthesis and insertion of new Na ⁺ pumps into the plasma membrane of certain epithelial cells.

  
  
• c.
  

  Na ⁺ pumps can be regulated by phosphorylation at a site other than the catalytic site.

  
  
• d.
  

  Na ⁺ pumps are electrogenic: They generate a current and normally contribute a few (e.g., 1–3) millivolts to the resting V _m .

  
  
• e.
  

  Most cells have two different Na ⁺ pumps that are the products of different genes: One is located in the plasma membrane and the other in the endoplasmic reticulum.

All of the following are true of transport ATPases EXCEPT:

• a.
  

  The Na ⁺ pump (Na ⁺ ,K ⁺ -ATPase) ultimately provides the energy for most secondary active transport mechanisms.

  
  
• b.
  

  The Na ⁺ ,K ⁺ -ATPase normally generates an inward ionic current.

  
  
• c.
  

  The gastric H ⁺ ,K ⁺ -ATPase can extrude protons from an intracellular environment with pH of 7.2 to a very acidic extracellular environment (pH 2–3).

  
  
• d.
  

  Wilson’s disease and Menkes’ disease are associated with genetic defects in two different copper-transporting ATPases.

  
  
• e.
  

  The multidrug resistance (MDR) transport proteins are ATPases that actively transport anticancer agents such as doxorubicin (Adriamycin) out of cells.

Inhibition of the Na ⁺ pump by ouabain can lead to all of the following EXCEPT:

• a.
  

  Swelling of skeletal muscle cells.

  
  
• b.
  

  Reduction of neurotransmitter (e.g., dopamine) reuptake at nerve terminals.

  
  
• c.
  

  Augmentation of Ca ²⁺ -dependent secretion of catecholamine by adrenal medullary cells.

  
  
• d.
  

  Augmentation of glucose and amino acid (e.g., alanine) absorption from the intestinal lumen.

  
  
• e.
  

  Cell acidification.

The Na ⁺ pump does all of the following EXCEPT:

• a.
  

  Helps regulate the glucose concentration in skeletal muscle.

  
  
• b.
  

  Contributes directly to the resting V _m by generating an outward ionic current.

  
  
• c.
  

  Contributes indirectly to the resting V _m by regulating [K ⁺ ] _i .

  
  
• d.
  

  Helps regulate Ca ²⁺ stores in the sarcoplasmic and endoplasmic reticulum and Ca ²⁺ signaling.

  
  
• e.
  

  Helps maintain cell volume.

The multidrug resistance (MDR) proteins are all of the following EXCEPT:

• a.
  

  Are members of the ATP-binding cassette superfamily of transporters.

  
  
• b.
  

  Transport proteins that may be upregulated in the presence of their substrates.

  
  
• c.
  

  Primary active transporters.

  
  
• d.
  

  Transport proteins that actively concentrate many types of drugs in cells.

  
  
• e.
  

  Transport proteins that underlie drug resistance to many anticancer agents.

Which one of the following statements about regulation of solute transport is TRUE:

• a.
  

  Insulin stimulates glucose uptake into skeletal muscle cells by increasing the number of Na ⁺ -glucose cotransporter molecules in the plasma membrane.

  
  
• b.
  

  Histamine stimulates the secretion of acid into the stomach lumen by increasing the number of H ⁺ , K ⁺ -ATPase molecules in the parietal cell basolateral membrane.

  
  
• c.
  

  Histamine stimulates the secretion of acid into the stomach lumen by increasing the number of Na ⁺ /H ⁺ exchanger molecules in the oxyntic cell apical membrane.

  
  
• d.
  

  Hepatocytes (liver cells) can import Cu ⁺ from plasma delivered from the gastrointestinal tract (via the hepatic portal vein), and can export Cu ⁺ into the bile as well as into the plasma (of the hepatic veins and inferior vena cava) for circulation to the periphery.

  
  
• e.
  

  The Na ⁺ /H ⁺ exchanger (NHE), with a coupling ratio of 1 Na ⁺ :1 H ⁺ , operates close to electrochemical equilibrium in most cells, since pH _o (∼7.2) is close to pH _i (∼7.4).

All of the following statements about Ca ²⁺ homeostasis are true EXCEPT:

• a.
  

  The free Ca ²⁺ concentration in the ER/SR ([Ca ²⁺ ] _ER/SR ) of quiescent (resting) cells is normally greater than 10 ⁻⁴ M.

  
  
• b.
  

  Most of the Ca ²⁺ in the lumen of the ER or SR is free Ca ²⁺ (i.e., not bound to proteins).

  
  
• c.
  

  [Ca ²⁺ ] _i in quiescent cells is normally approximately 10 ⁻⁷ M.

  
  
• d.
  

  Partial Na ⁺ pump inhibition can induce a large increase in [Ca ²⁺ ] _ER/SR despite a very small increase in [Na ⁺ ] _i .

  
  
• e.
  

  The plasma membrane Ca ²⁺ pump (PMCA) plays an important role in maintaining [Ca ²⁺ ] _i in quiescent cells.

A 25-year-old man comes to your office with a chief complaint that his muscles are stiff after he exercises. On physical examination you find nothing remarkable. However, when you ask him to flex and extend his arms rapidly and repeatedly, you notice that he soon slows down and his muscles seem to remain tense and contracted longer and longer. He reports that his older brother has a similar problem. The impaired skeletal muscle relaxation could be explained by a defect causing reduced activity of which one of the following skeletal muscle channels/transporters?

• a.
  

  Ryanodine receptors (SR Ca ²⁺ -release channels).

  
  
• b.
  

  Dihydropyridine receptors (L-type Ca ²⁺ channels).

  
  
• c.
  

  Plasma membrane Ca ²⁺ pump (PMCA).

  
  
• d.
  

  SR Ca ²⁺ pump (SERCA).

  
  
• e.
  

  Na ⁺ /Ca ²⁺ exchanger.

All of the following statements about transepithelial cell transport are true EXCEPT:

• a.
  

  The main driving force for Cl ⁻ reabsorption in the small intestine and the renal proximal tubule cells is the –3 to –5 mV (lumen negative) transepithelial electrical potential gradient.

  
  
• b.
  

  Most of the Cl ⁻ reabsorbed in the renal proximal tubules is transported through the cells (i.e., by the transcellular pathway).

  
  
• c.
  

  Pancreatic exocrine secretions are a major source of the Na ⁺ that is used to drive Na ⁺ -coupled solute transport across intestinal cell apical membranes.

  
  
• d.
  

  Net transport of many solutes across epithelia is ultimately driven by the Na ⁺ pump in the basolateral membrane.

  
  
• e.
  

  Net solute transport across epithelia depends on the presence of different transporters (carriers, pumps, or channels) in the apical and basolateral membranes.

All of the following statements about water (re)absorption across epithelia are true EXCEPT:

• a.
  

  Net water transport may occur by active transport of water molecules.

  
  
• b.
  

  Net water transport is always coupled to solute transport.

  
  
• c.
  

  Net water transport across leaky epithelia is always driven by an osmotic gradient.

  
  
• d.
  

  Water absorbed across tight epithelia normally passes through the epithelial cells (i.e., it occurs through the transcellular route).

  
  
• e.
  

  Antidiuretic hormone (ADH) promotes water transport across some tight epithelia by promoting the insertion of aquaporins (water channels) into the apical membrane of the epithelial cells.

Secretory diarrhea is dependent on which one of the following cAMP-mediated mechanisms:

• a.
  

  Increased activation of Cl ⁻ channels in the apical membrane of intestinal epithelial cells.

  
  
• b.
  

  Increased activation of Cl ⁻ channels in the basolateral membrane of intestinal epithelial cells.

  
  
• c.
  

  Increased insertion of aquaporins (water channels) into the apical membrane of intestinal epithelial cells.

  
  
• d.
  

  Increased insertion of aquaporins into the basolateral membrane of intestinal epithelial cells.

  
  
• e.
  

  Inhibition of the Na ⁺ pump in the basolateral membrane of intestinal epithelial cells.

All of the following statements about gap junction channels are true EXCEPT:

• a.
  

  They are formed by two hemichannels.

  
  
• b.
  

  They connect two neurons at an electrical synapse.

  
  
• c.
  

  They allow current to flow directly from one cell to another.

  
  
• d.
  

  They allow the passage of monovalent ions, but not other molecules.

  
  
• e.
  

  They allow rapid communication because of a negligible synaptic delay.

The size of the EPP at the NMJ can be reduced by all of the following EXCEPT:

• a.
  

  Decreasing the concentration of ACh in synaptic vesicles.

  
  
• b.
  

  Inhibiting the enzyme acetylcholinesterase.

  
  
• c.
  

  Decreasing the Na ⁺ permeability of nAChRs.

  
  
• d.
  

  Decreasing [Ca ²⁺ ] _o .

  
  
• e.
  

  Blocking nAChRs with curare.

All of the following events contribute to the synaptic delay at chemical synapses EXCEPT:

• a.
  

  The EPP causing voltage-gated Na ⁺ channels to open.

  
  
• b.
  

  The presynaptic AP causing voltage-gated Ca ²⁺ channels to open.

  
  
• c.
  

  ACh diffusing across the synaptic cleft.

  
  
• d.
  

  ACh opening nAChR channels in the postsynaptic membrane.

  
  
• e.
  

  Ca ²⁺ entering the presynaptic cell and triggering transmitter release.

All of the following contribute to the size of MEPPs at the NMJ EXCEPT:

• a.
  

  The amount of ACh stored in a synaptic vesicle.

  
  
• b.
  

  [Ca ²⁺ ] _o .

  
  
• c.
  

  The activity of acetylcholinesterase.

  
  
• d.
  

  The conductance of nAChR channels in the postsynaptic membrane.

  
  
• e.
  

  The open probability of nAChR channels in the postsynaptic membrane.

All of the following statements about chemical synapses are true EXCEPT:

• a.
  

  High concentrations of neurotransmitters are stored in synaptic vesicles in the presynaptic nerve terminal.

  
  
• b.
  

  At an active zone, synaptic vesicles must be “docked” before neurotransmitters can be released.

  
  
• c.
  

  Neurotransmitters are released by fusion of synaptic vesicles with the cell membrane at the nerve terminal.

  
  
• d.
  

  Transporters are the predominant mechanism for removing neurotransmitters from the synaptic cleft.

  
  
• e.
  

  Released neurotransmitters can trigger the opening of ion channels to activate the postsynaptic neuron.

All of the following statements about transmitter release are true EXCEPT:

• a.
  

  Synaptotagmin is a protein on the synaptic vesicle that is required for neurotransmitter release.

  
  
• b.
  

  Ca ²⁺ ions trigger neurotransmitter release by activating synaptotagmin.

  
  
• c.
  

  Toxins such as α-latrotoxin and botulinum toxin (BoTox) block synaptic transmission by inhibiting neurotransmitter release.

  
  
• d.
  

  SNAP and SNARE proteins are essential components of the neurotransmitter release machinery in the nerve terminal.

  
  
• e.
  

  After neurotransmitter release, the synaptic vesicle membrane is immediately retrieved back into the nerve terminal.

All of the following statements about short-term synaptic plasticity are true EXCEPT:

• a.
  

  Synaptic depression, synaptic facilitation, and posttetanic potentiation are all forms of short-term plasticity.

  
  
• b.
  

  Synaptic depression is fully explained by depletion of releasable synaptic vesicles.

  
  
• c.
  

  Ca ²⁺ ions are essential for induction of synaptic facilitation.

  
  
• d.
  

  In synaptic depression, the second of a pair of stimuli evokes a smaller postsynaptic response.

  
  
• e.
  

  Posttetanic potentiation requires a rise of [Ca ²⁺ ] _i in the presynaptic terminal.

All of the following statements are true about nAChRs EXCEPT:

• a.
  

  nAChR channels are permeable to both Na ⁺ and K ⁺ .

  
  
• b.
  

  Prolonged exposure of nAChRs to ACh causes desensitization.

  
  
• c.
  

  Opening of nAChR channels at the NMJ produces an EPP.

  
  
• d.
  

  nAChRs can be activated by nicotine.

  
  
• e.
  

  The E _rev of nAChR channels is normally close to E _Na .

The main excitatory neurotransmitter in the brain is:

• a.
  

  Acetylcholine.

  
  
• b.
  

  Norepinephrine.

  
  
• c.
  

  Glutamate.

  
  
• d.
  

  Glycine.

  
  
• e.
  

  Dopamine.

Unconventional neurotransmitters such as endocannabinoids:

• a.
  

  Are stored in small translucent synaptic vesicles.

  
  
• b.
  

  Are stored in large dense-core vesicles.

  
  
• c.
  

  Are stored in small dense-core vesicles.

  
  
• d.
  

  Are released immediately after synthesis.

  
  
• e.
  

  Activate ionotropic receptors.

All of the following statements about glutamate receptors are trued EXCEPT:

• a.
  

  AMPARs mediate fast excitatory synaptic transmission.

  
  
• b.
  

  NMDAR activation requires a coagonist.

  
  
• c.
  

  KARs are monovalent cation-selective channels.

  
  
• d.
  

  NMDAR channels are blocked by benzodiazepines.

  
  
• e.
  

  Activation of mGluRs located on presynaptic terminals may modulate neurotransmitter release.

All of the following statements about ionotropic glutamate receptors are true EXCEPT:

• a.
  

  All ionotropic glutamate receptors are channels permeable to both Na ⁺ and K ⁺ .

  
  
• b.
  

  NMDAR channels are blocked by extracellular Mg ²⁺ at negative V _m .

  
  
• c.
  

  In response to glutamate, NMDAR channels open more rapidly than AMPAR channels.

  
  
• d.
  

  NMDAR channels are permeable to Ca ²⁺ .

  
  
• e.
  

  NMDAR channels conduct outward current better than inward current.

All of the following statements about inhibitory synaptic transmission are true EXCEPT:

• a.
  

  GABA receptor activation can increase Cl ⁻ conductance.

  
  
• b.
  

  GABA receptor activation can decrease Ca ²⁺ conductance.

  
  
• c.
  

  GABA receptor activation can increase K ⁺ conductance.

  
  
• d.
  

  Ionotropic GABA receptors are targets of benzodiazepines.

  
  
• e.
  

  A genetic defect in GABA receptors is responsible for human startle disease.

All of the following statements about neurotransmission are true EXCEPT:

• a.
  

  ADP is a cotransmitter that is released with norepinephrine.

  
  
• b.
  

  Adenosine activates P1 receptors and indirectly opens inward-rectifying K ⁺ channels.

  
  
• c.
  

  All P1 purinergic receptors are metabotropic and are members of the G-protein-coupled receptor family.

  
  
• d.
  

  The endocannabinoid 2-arachidonoylglycerol (2-AG) is released by activation of metabotropic glutamate receptors.

  
  
• e.
  

  The endocannabinoid 2-arachidonoylglycerol (2-AG) is a retrograde transmitter that inhibits transmitter release at glutamatergic synapses.

All of the following statements about long-term synaptic plasticity are true EXCEPT:

• a.
  

  Long-term potentiation (LTP) and long-term depression (LTD) are persistent changes in the efficiency of neurotransmission at a synapse.

  
  
• b.
  

  Once induced by synaptic stimulation, LTP and LTD can persist for at least days to weeks.

  
  
• c.
  

  A rise in [Ca ²⁺ ] _i is necessary for induction of all forms of LTP and LTD.

  
  
• d.
  

  Ca ²⁺ influx through NMDAR channels can activate LTP or LTD.

  
  
• e.
  

  The frequency of stimulation determines whether LTP or LTD is induced at a synapse.

Which of the following statements about the structure of skeletal muscle is FALSE?

• a.
  

  Thick filaments interdigitate with thin filaments, so that each thick filament is surrounded by a hexagonal array of thin filaments.

  
  
• b.
  

  Bundles of thick and thin filaments run obliquely across the cell.

  
  
• c.
  

  Thick filaments are composed mostly of myosin.

  
  
• d.
  

  Thin filaments are composed of actin, tropomyosin, troponin, and nebulin.

  
  
• e.
  

  Surrounding each myofibril is an extensive membrane-enclosed intracellular compartment, the sarcoplasmic reticulum.

In the presence of high [Ca ²⁺ ] _i all of the following steps occur in the cross-bridge cycle in skeletal muscle EXCEPT:

• a.
  

  ATP binds to myosin and thus causes the cross-bridge to detach.

  
  
• b.
  

  With ADP and Pi bound to the myosin head, myosin binds to actin.

  
  
• c.
  

  When ATP is hydrolyzed to ADP and Pi, the angle between the myosin head and the thin filament changes from 45 to 90 degrees.

  
  
• d.
  

  The release of ADP generates the power stroke.

  
  
• e.
  

  Force is generated when the angle between the myosin head and the thin filament changes from 90 to 45 degrees.

All of the following are features of both skeletal and cardiac muscles EXCEPT:

• a.
  

  Individual muscle cells are electrically connected through gap junction channels.

  
  
• b.
  

  Ca ²⁺ ions initiate contraction by binding to troponin C.

  
  
• c.
  

  The contractile elements are organized in sarcomeres.

  
  
• d.
  

  Force is generated by a sliding filament mechanism.

  
  
• e.
  

  In resting muscle cells, cross-bridges cannot form because tropomyosin covers the myosin-binding sites on actin.

In skeletal muscle the activation of contraction by Ca ²⁺ involves the regulatory proteins tropomyosin and troponin in which of the following ways?

• a.
  

  When [Ca ²⁺ ] _i rises into the micromolar range, Ca ²⁺ binds to troponin C and weakens the bond between troponin I and actin.

  
  
• b.
  

  Troponin T links the troponin complex to tropomyosin.

  
  
• c.
  

  Tropomyosin moves on the thin filament to either cover or expose myosin-binding sites on actin.

  
  
• d.
  

  a, b, and c are all true.

  
  
• e.
  

  Only b and c are true.

All of the following are true of both skeletal and cardiac muscle contraction EXCEPT:

• a.
  

  Contraction is initiated by a depolarization of the surface membrane.

  
  
• b.
  

  Almost all of the Ca ²⁺ that activates the contraction is pumped back into the SR by SERCA.

  
  
• c.
  

  L-type Ca ²⁺ channels (DHPRs) in the surface membrane are activated by depolarization.

  
  
• d.
  

  Ca ²⁺ is released from the SR into the cytoplasm through open Ca ²⁺ -release channels (RyRs) in the SR.

  
  
• e.
  

  Ca ²⁺ -release channels in the SR are opened at specialized junctions between SR and T-tubule membranes.

The activation of Ca ²⁺ release from the SR during a contraction in skeletal muscle:

• a.
  

  Occurs by the same mechanism as in cardiac muscle.

  
  
• b.
  

  Is caused by Ca ²⁺ entering the cell through L-type Ca ²⁺ channels in the surface membrane.

  
  
• c.
  

  Occurs through Ca ²⁺ -release channels opened by IP ₃ binding.

  
  
• d.
  

  Is independent of V _m .

  
  
• e.
  

  None of the above.

Which of the following is FALSE?

• a.
  

  The opening of RyRs in cardiac muscle involves Ca ²⁺ -induced Ca ²⁺ release.

  
  
• b.
  

  The activity of both the Na ⁺ /Ca ²⁺ exchanger and SR Ca ²⁺ pump (SERCA) decreases [Ca ²⁺ ] _i and causes the relaxation of cardiac muscle.

  
  
• c.
  

  Extracellular Ca ²⁺ is required for E-C coupling in cardiac muscle.

  
  
• d.
  

  All of the Ca ²⁺ that activates cardiac muscle contraction comes from the SR.

  
  
• e.
  

  The Ca ²⁺ release through Ca ²⁺ release channels can be visualized as Ca ²⁺ “sparks.”

Which of the following statements about FF (fast, fatigable), FR (fast, fatigue-resistant), and S (slow) motor units in skeletal muscle is FALSE?

• a.
  

  S motor units generate the smallest forces and do not fatigue.

  
  
• b.
  

  Whole muscle often contains mixtures of FF, FR, and S motor units.

  
  
• c.
  

  A motor unit is a single skeletal muscle cell and the α motor neuron that innervates it.

  
  
• d.
  

  FR motor units are more resistant to fatigue than FF motor units.

  
  
• e.
  

  FF motor units generate the largest tetanic forces and are usually recruited after S and FR motor units.

The force generated by cardiac muscle can be increased by all of the following EXCEPT:

• a.
  

  Increasing the duration of the cardiac action potential.

  
  
• b.
  

  Inhibiting Na ⁺ /Ca ²⁺ exchangers in the plasma membrane.

  
  
• c.
  

  Activating β-adrenergic receptors in cardiac muscle.

  
  
• d.
  

  Increasing the end-diastolic volume of the heart.

  
  
• e.
  

  Increasing the frequency of stimulation of the heart to generate a tetanic contraction.

In a pure isometric contraction the force generated by whole skeletal muscle can be increased by all of the following EXCEPT:

• a.
  

  Increasing the number of motor units that are activated.

  
  
• b.
  

  Increasing the frequency of stimulation of the muscle.

  
  
• c.
  

  Increasing the sarcomere length from 1.4 to 1.6 μm.

  
  
• d.
  

  Increasing the sarcomere length from 2.4 to 3.0 μm.

  
  
• e.
  

  Decreasing the rate of Ca ²⁺ uptake by SERCA into the SR.

All of the following are true of the relationship between isotonic force and velocity of shortening in skeletal muscle EXCEPT:

• a.
  

  As the isotonic force generated by the muscle increases, the velocity of shortening decreases.

  
  
• b.
  

  The maximum velocity of shortening ( V ₀ ) occurs when the muscle shortens with no attached load.

  
  
• c.
  

  V ₀ is a reflection of the maximum rate of cross-bridge cycling.

  
  
• d.
  

  V ₀ is inversely proportional to myosin ATPase activity.

  
  
• e.
  

  If the load attached to the muscle is greater than the maximum force the muscle can generate, the velocity of shortening is zero.

The maximum force in a twitch contraction in skeletal muscle is smaller than the maximum tetanic force because:

• a.
  

  The amount of Ca ²⁺ released during a twitch is not enough to saturate all the troponin C binding sites.

  
  
• b.
  

  During a twitch there is not enough time to fully stretch series elastic elements in the muscle.

  
  
• c.
  

  [Ca ²⁺ ] _i remains elevated for a longer time during a tetanus.

  
  
• d.
  

  a, b, and c are all true.

  
  
• e.
  

  Only b and c are true.

All of the following statements about malignant hyperthermia (MH) are true EXCEPT:

• a.
  

  MH is triggered by exposure to volatile, halogenated anesthetics.

  
  
• b.
  

  Dihydropyridines (e.g., nifedipine) are used to prevent attacks of MH.

  
  
• c.
  

  An episode of MH is characterized by a sustained increase in [Ca ²⁺ ] _i in skeletal muscle.

  
  
• d.
  

  Most cases of MH are associated with a point mutation in the gene that encodes the skeletal muscle RyR.

  
  
• e.
  

  In an episode of MH, continuous cross-bridge cycling and SERCA activity produce an increase in body temperature that can be fatal.

Which one of the following statements is FALSE?

• a.
  

  In an isotonic contraction the velocity of shortening is constant.

  
  
• b.
  

  In an isometric contraction the muscle generates force and then relaxes at constant length.

  
  
• c.
  

  In an isotonic contraction the muscle shortens against a constant load.

  
  
• d.
  

  Under physiological conditions most skeletal muscle contractions are partly isotonic and partly isometric.

  
  
• e.
  

  When skeletal muscle is activated with an attached load, the first phase of the contraction is isometric force development.

All of the following are true EXCEPT:

• a.
  

  Smooth muscles do not exhibit the striation patterns observed in skeletal muscle, because the thick and thin filament bundles are not in register.

  
  
• b.
  

  Smooth muscle, like skeletal muscle, requires troponin C (TnC) for contractile activation.

  
  
• c.
  

  The dense bodies of smooth muscles are analogous to the Z lines of skeletal muscle, because both are composed primarily of α-actinin.

  
  
• d.
  

  The dense bodies of smooth muscles are analogous to the Z lines of skeletal muscle, because the thin filaments are inserted into the dense bodies.

  
  
• e.
  

  In saccular organs such as the urinary bladder, both longitudinal and lateral forces cause relatively uniform contraction of the organ wall.

Smooth muscle contraction can be activated by all of the following EXCEPT:

• a.
  

  Ca ²⁺ binding to calmodulin.

  
  
• b.
  

  Ca ²⁺ binding to SERCA.

  
  
• c.
  

  Phosphorylation of myosin regulatory light chain (RLC).

  
  
• d.
  

  IP ₃ .

  
  
• e.
  

  Ca ²⁺ binding to RyRs.

Smooth muscle relaxation is promoted by all of the following EXCEPT:

• a.
  

  Dephosphorylation of myosin regulatory light chain (RLC).

  
  
• b.
  

  Elevating the concentration of cAMP in the smooth muscle cytoplasm.

  
  
• c.
  

  Decreasing the activity of myosin RLC phosphatase.

  
  
• d.
  

  Phosphorylation of myosin light chain kinase.

  
  
• e.
  

  Opening K _Ca channels.

Mechanisms involved in the activation of smooth muscles may include all of the following EXCEPT:

• a.
  

  Depolarization initiated by some neurotransmitters such as ACh.

  
  
• b.
  

  ACh-induced release of nitric oxide (NO).

  
  
• c.
  

  Release of Ca ²⁺ from the SR.

  
  
• d.
  

  Pharmacomechanical coupling that involves little or no change in V _m .

  
  
• e.
  

  Ca ²⁺ -independent changes in the sensitivity of the contractile apparatus to Ca ²⁺ .

Activation of smooth muscle differs from that of skeletal muscles in that:

• a.
  

  Smooth muscles are never activated by membrane depolarization.

  
  
• b.
  

  Smooth muscles are not dependent on SR Ca ²⁺ release.

  
  
• c.
  

  Smooth muscles are activated by a troponin-tropomyosin–regulated mechanism.

  
  
• d.
  

  Smooth muscles generate much less force per unit cross-sectional area (= “stress”).

  
  
• e.
  

  Smooth muscle contraction velocity is slower.

All of the following are true of tonic smooth muscles EXCEPT:

• a.
  

  The unitary actin-myosin cross-bridge force is much smaller than in skeletal muscle.

  
  
• b.
  

  Smooth muscle cross-bridge attachments last several times longer than skeletal muscle cross-bridge attachment.

  
  
• c.
  

  Compared with skeletal muscle, a much larger fraction of the smooth muscle actin-myosin cross-bridges are attached at any time.

  
  
• d.
  

  Tonic smooth muscles can maintain contraction with little consumption of ATP.

  
  
• e.
  

  The rate of ADP dissociation from myosin in smooth muscles is very slow when the cross-bridges are attached.