Chapter 13: Membrane Channels and Pumps

secondary

A ______ transporter uses the favorable flow of one ion to drive the unfavorable movement of another.

intermediate

A coupled reaction uses a common ______ to transfer energy from one side of the reaction to the other.

high, calcium, low

A gap junction, once formed, tends to stay open for seconds to minutes. They are closed by (LOW / HIGH) concentrations of ______ ion and by (LOW / HIGH) pH.

digitalis, increasing

A group of steroid medicines extracted from foxglove plants are called ______. They are often used to treat congestive heart failure by (DECREASING / INCREASING) muscle contraction.

Binds ATP (specifically the nucleotide, hence the name N domain)

A large cytoplasmic headpiece constitutes nearly half the molecular weight of SERCA and consists of three distinct domains, each with a particular function. What is the function of the N domain?

symporter

A(n) ______ is a type of secondary transporter that uses the flow of one species to drive the flow of a different species in the SAME DIRECTION across the membrane.

antiporter

A(n) ______is a type of secondary transporter that couples the downhill flow of one species to the uphill flow of another in the OPPOSITE DIRECTION across the membrane.

ball-and-chain

According to the ______-______-______ model, the first 20 residues of the K+ channel form a cytoplasmic unit that is attached to a flexible segment of the polypeptide. Movement of this unit causes channel inactivation.

open (Hence, the channel opens for only a brief interval before it undergoes inactivation by occlusion.)

According to the ball-and-chain model, when the channel is (OPEN / CLOSED), the ball quickly finds a complementary site in the pore and occludes it.

closed

According to the ball-and-chain model, when the channel is (OPEN/CLOSED), the ball rotates freely in the aqueous solution.

small

Because a sodium ion is too (SMALL / LARGE) to interact favorably with the selectivity filter of the potassium channel, the free energy of desolvation cannot be compensated and the sodium ion does not pass through the channel.

2, alpha-helices

Binding of ______ acetylcholine molecule(s) to the extracellular domain of an acetylcholine receptor channel causes a structural alteration that initiates rotations of the ______-______ lining the membrane-spanning pore.

water

Both the opening to the outside and the central cavity of the potassium channel pore are filled with ______, and a K+ ion can fit into the pore without losing its shell of bound water molecules until it reaches a diameter of 3 Angstroms.

sarcoplasmic reticulum

Ca2+-ATPASE (SERCA) maintains a Ca2+ concentration of approximately 0.1 uM in the cytoplasm compared with 1.5 mM in the ______ ______, a nearly 15000 fold concentration difference.

-60

Closing of Na+ channels causes the membrane potential to reach approximately ______ mV in 1-2 s.

Phosphate removal by hydrolysis (E2 conversion)

Digitalis inhibits the Na+/K+ pump by blocking what process in its mechanism?

K+ ions are obtained in the diet, where as channel-blocking peptides require synthesis.

Evolutionarily, why does it make sense for scorpions to release a K+ ion prevenom before it delivers venom containing channel blocking peptides?

No (When C2 > C1, ∆G > 0, and the process is unfavorable.)

Free energy stored in concentration gradients can be quantified by the equation depicted in the figure. If the concentration at the origin (c1) is less than the concentration at the destination (c2) will the process be favorable, assuming a negligible charge/potential effect?

favorable (Z is positive making ∆V negative and thus ∆G<0 and the process is favorable.)

Free energy stored in concentration gradients can be quantified by the equation depicted in the figure. If you are moving a positive charge to a negative one, will the process be favorable, assuming a negligible concentration effect?

increase (inhibit Na+/K+ pump, inactivate Na+/Ca2+ exchanger, Ca2+ is not transport out of cell)

If a person were treated with digitalis, would you expect an increase or decrease in their intracellular calcium levels?

E1

In the ______ conformation, SERCA can bind ATP.

E2-P

In the ______ conformation, the Ca2+-binding sites become disrupted and the calcium ions are released to the side of the membrane opposite that at which they entered and ion transport has been achieved.

free-energy cost of dehydration is high

Ions having a radius larger than 1.5 Angstroms cannot pass into the narrow diameter (3 Angstoms) of the selectivity filter of the K+ channel. How then is Na+, which has an ionic radius of 0.95 Angstroms, rejected?

desolvation

K+ energy has a lower ______ energy at -55 kcal/mol compared to Na+ at -72 kcal/mol.

Introduction of K+ in the extracellular space will result in permanent Na+ inactivation since the concentration gradient for K+ will have been destroyed. The membrane will remain in the absolute refractory state and the membrane becomes in-excitable.

Na+ channels remain inactivated until membrane potential drops below threshold in the repolarization phase. With this information, what would you expect to happen if KCl was introduced into the extracellular space?

30

Opening of Na+ channels causes the membrane potential to reach approximately ______ mV in 1 ms.

tetrameric

Potassium channels have a ______ structure in which identical protein subunits associate to form a complex arranged around a central ion conducting pore.

10

SERCA is a single 110-kd polypeptide with a transmembrane domain consisting of ______ alpha helices. The transmembrane domain includes sites for binding two calcium ions.

It would indirectly inhibit the Na+/Ca2+ exchanger. Since the Na+/K+ pump uses ATP to set up ion gradients, without its action the transport of 3 Na+ would not be favorable.

Suppose a drug targets the Na+/K+ pump. How would this affect the Na+/Ca2+ exchanger?

positive

The "ball" domains, include substantial regions of _______ charge. This causes them to be pulled into the open channel, blocking further ion conductance.

1, out of

The Na+/Ca2+ exchanger moves ______ Ca2+ (INTO/OUT OF) the cell.

3, into

The Na+/Ca2+ exchanger moves ______ Na+ (INTO/OUT OF) the cell.

3 Na+, 2 K+

The Na+/K+ -ATPase is a solute pump that pumps: ______ (# ions) _____ ( type ion) OUT of cells while pumping _____ ______ INTO cells, both against their concentration gradients. It was discovered by Jens Skou in 1957 who received the Nobel Prize in 1997.

phosphorylaspartate

The ______ residue is hydrolyzed to release inorganic phosphate (step 5).

ligand

The acetylcholine receptor channel is a type of ______-gated ion channel.

inside (The concentration of K+ inside the cell is 157 mM and 4 mM outside. This is nearly a 40 fold difference.)

The concentration of K+ is greater (INSIDE / OUTSIDE) of the cell.

outside (The concentration of Na+ outside of the cell is 143 mM and 14 mM inside the cell. This is nearly a 10 fold difference.)

The concentration of Na+ is greater (INSIDE / OUTSIDE) of the cell.

selectivity filter

The energy cost of dehydrating a potassium ion is compensated by favorable interactions with carbonyl groups in the ______ ______.

unfavorable (ΔG > 0)

The movement of 1 Ca2+ out of the cell by the Na+/Ca2+ exchanger is thermodynamically (FAVORABLE / UNFAVORABLE).

favorable (ΔG < 0)

The movement of 3 Na+ into the cell by the Na+/Ca2+ exchanger is thermodynamically (FAVORABLE / UNFAVORABLE).

sodium

The opening of the ligand-gated acetylcholine receptor channel changes the potential from -60 mV to -40 mV. This stimulates the opening of voltaged-gated _______ channels.

Asp 351

The phosphoryl group of bound ATP is then transferred to ______ on the P domain.

synaptic cleft, motor

The presynaptic membrane of a synapse is separated from the postsynaptic membrane by a gap of about 50 nm called the ______ ______. In the case of acetylcholine, the presynaptic membrane is from a ______ neuron.

eversion

The process of interconverting the E1 and E2 conformations is sometimes referred to as ______ (steps 4 and 6 in figure).

4, electrostatic repulsion

The selectivity filter has ______ binding sites. Hydrated potassium ions can enter these sites, one at a time, losing their hydration shells. When two ions occupy adjacent sites, ______ _____ forces them apart. Thus, as ions enter the channel from one side, other ions are pushed out the other side.

voltage

The sodium channel is a type of ______-gated channel.

antiporter

The sodium-calcium exchanger is a(n) ______ secondary transporter that removes calcium from cells.

True

True or False: All polar molecules with a mass of less than about 1 kd can readily pass through gap junctions.

True

True or False: Carbonyl groups interact better with potassium contributing to its selectivity over potassium.

False (The ΔG for ion transport is not favorable. It is the paired hydrolysis of ATP that makes it favorable. ΔG = +10 kcal/mol for ion transport, Δ= -12 kcal/mol, ΔG overall = -2 kcal/mol)

True or False: Ion transport by active transport is thermodynamically favorable.

False (Shortening the chain speeds inactivation because the ball finds its target more quickly. Conversely, lengthening the chain slow inactivation.)

True or False: Lengthening the chain speeds inactivation according to the ball-and-chain model.

False (K+ has a larger ionic radius at 1.33 Angstroms compared to the 0.95 Angstrom radius of Na+.)

True or False: Na+ has a larger ionic radius than K+ and thus does not fit into the channel pore.

False (It takes approximately 1 ms for the membrane to depolarize but 1-2 s for the membrane to repolarize.)

True or False: Repolarization is faster than depolarization.

True

True or False: The Na+/Ca2+ exchanger has a lower Ca2+ affinity than SERCA.

False (The Na+/Ca2+ exchanger is much faster, working at 2000 /s compared to 30 /s.)

True or False: The Na+/Ca2+ exchanger is much slower than SERCA.

False (The ΔG for ion transport is +10 kcal/mol and the ΔG for ATP hydrolysis is -12 kcal/mol making the overall Δ equal to -2, and thus thermodynamically favorable.)

True or False: The Na+/K+-ATPase pump is thermodynamically unfavorable.

True

True or False: The velocity of ions is much faster for channels than for pumps.

4, 1, 2, 6, 3, 5

Use the figure to order the steps in Ca2+-ATPase transport of calcium through the membrane. 1.) ATP binding 2.) ATP cleavage with the transfer of a phosphoryl group to Asp 351 on the enzyme 3.) Hydrolysis of the phosphorylaspartate residue 4.) Ca2+ binding from the cytoplasm 5.) Eversion to prepare for the binding of Ca2+ from cytoplasm 6.) ADP release and eversion of the enzyme to release Ca2+ on the opposite side of the membrane

carbonyl groups

What are the pink atoms lining the potassium channel selectivity filter?

K+ ions

What does scorpion "prevenom" contain that allows the paralysis of small prey?

channel blocking peptides

What does scorpion venom contain that allows it to paralyze larger prey?

Serves as an actuator (Links changes in the N and P domains to the transmembrane part of the enzyme.)

What is the function of the A domain in the head group of SERCA?

Gets phosphorylated (accepts the phosphoryl group on a conserved aspartate residue)

What is the function of the P domain in the head group of SERCA?

E1-(Ca2+)2

What is the overall enzyme conformation of Ca2+-ATPase in its unphosphorylated state at the beginning of its catalytic cycle?

simple diffusion

What mode of transportation do neutral and nonpolar species utilize to cross membranes?

active transport (via pump)

What mode of transportation do polar species utilize to move against their concentration gradients?

channel

What mode of transportation do polar species utilize to move in a favorable direction?

ADP release

What triggers the conformational change of SERCA from its E1 state to E2?

Release of phosphate (The phosphoryl group on the P domain stabilizes the E2 conformation.)

What triggers the conformational change of SERCA from its E2 state to E1?

leucine (large and hydrophobic; ions cannot pass)

When the acetylcholine receptor channel is closed, the amino acid sequences of the helices in the membrane point to the presence of ______ residues.

serine (small and polar; ions can pass)

When two acetylcholines bind the acetylcholine receptor channel, the alpha helices rotate to expose ______ residues which allow the passage of Na+ and K+ ions.

SERCA (Sarcoplasmic Reticulum Ca2+-ATPase)

______ (use acronym), a P-type ATPase, transports Ca2+ out of the cytoplasm and into the sarcoplasmic reticulum of muscle cells.

Reaction coupling

______ ______ is the process of pairing a reaction with a positive ∆G with a reaction with a negative ∆G of higher magnitude.

Gap junctions

______ _______, also known as cell-to-cell channels, serve as passageways between the interiors of contiguous cells.

P-type ATPases

______-______ _______ are a large family of membrane proteins that use ATP to move ions in a thermodynamically unfavorable direction through active transport.