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What does ΔG < 0 mean?
Transport is energetically favorable; the solute moves down its gradient.
What does ΔG > 0 mean?
Transport is energetically unfavorable alone and needs energy coupling.
What is the free-energy equation for an uncharged solute moving inward?
ΔG = RT ln([A]in/[A]out).
What two factors determine an ion's electrochemical gradient?
The concentration gradient and membrane potential.
What is simple diffusion?
Direct movement through the lipid bilayer without transport proteins.
What is facilitated diffusion?
Passive movement down a gradient through a membrane protein.
How do channels and carrier proteins differ?
Channels form pathways; carriers bind solutes and change conformation.
What is primary active transport?
Transport directly coupled to energy, usually ATP hydrolysis.
What is secondary active transport?
Uphill transport powered by another solute moving downhill.
What is a channel-forming ionophore?
A molecule that forms a membrane-spanning pore for ion passage.
How does valinomycin shield K⁺ from the lipid bilayer?
Six inward-facing ester carbonyl oxygens coordinate K⁺; nonpolar groups face outward.
What is KcsA?
A bacterial K⁺ channel made of four identical subunits.
What determines KcsA selectivity for K⁺ over Na⁺?
Precisely positioned carbonyl oxygens and favorable K⁺ coordination energetics.
What maintains high intracellular K⁺ and high extracellular Na⁺?
The Na⁺/K⁺-ATPase.
What two forces act on K⁺ at rest?
The concentration gradient drives K⁺ outward; negative voltage attracts it inward.
What is the approximate neuronal resting membrane potential?
−70 mV.
What is the approximate action-potential threshold?
−55 mV.
What causes the rapid upstroke of an action potential?
Opening of voltage-gated Na⁺ channels and Na⁺ influx.
What causes action-potential repolarization?
Na⁺ channel inactivation and increased K⁺ efflux.
Why does after-hyperpolarization occur?
K⁺ channels remain open briefly, making the membrane more negative.
Which Kv segment acts as the voltage sensor?
S4, which contains multiple positively charged residues.
What does the S4–S5 linker do?
It couples voltage-sensor movement to the S6 activation gate.
Which Kv regions form the pore and selectivity filter?
S5–S6 form the pore; the P-loop contains the K⁺ selectivity filter.
What are the two major functions of ClC family members?
Some are passive Cl⁻ channels; others exchange Cl⁻ and H⁺.
What is ClC-1's role in skeletal muscle?
High resting Cl⁻ conductance helps stabilize membrane potential.
Why can extracellular K⁺ accumulation cause later depolarization?
It weakens the outward K⁺ gradient, making Eₖ less negative.
What is an aquaporin?
A membrane protein that enables rapid passive water transport.
How do aquaporins prevent proton transport?
NPA motifs reorient water, interrupting hydrogen-bond continuity; the filter excludes H⁺.
What is a gap junction?
A channel directly connecting the cytoplasms of adjacent cells.
What passes through gap junctions?
Ions and small metabolites or signals, but not large macromolecules.
How do GLUT transporters move glucose?
Facilitated diffusion using an alternating-access mechanism.
Why does glucose phosphorylation support continued uptake?
Glucose-6-phosphate formation keeps free intracellular glucose low.
Why do carrier-mediated transport rates saturate?
A finite number of carriers has a limited turnover rate.
How does simple diffusion differ kinetically from carrier-mediated transport?
Simple diffusion is approximately gradient-proportional; carrier transport saturates.
What is uniport?
Transport of one solute type across a membrane, such as GLUT1.
What is symport?
Coupled movement of different solutes in the same direction.
What is antiport?
Coupled movement of different solutes in opposite directions.
Do uniport, symport, and antiport specify energy requirements?
No; they describe transport organization, not energy use.
What defines a P-type ATPase?
A transient ATP-dependent phosphorylation of a conserved Asp residue.
What do E1 and E2 mean in P-type ATPases?
States with different ion-binding affinities and membrane accessibility.
What is the Na⁺/K⁺-ATPase stoichiometry?
Per ATP: 3 Na⁺ out and 2 K⁺ in.
Why is Na⁺/K⁺-ATPase electrogenic?
Each cycle moves one net positive charge outward.
Why is Na⁺/K⁺-ATPase important for secondary active transport?
It maintains the Na⁺ electrochemical gradient used by cotransporters.
Where is SERCA located?
In the sarcoplasmic/endoplasmic reticulum membrane.
What does SERCA transport per ATP-driven cycle?
2 Ca²⁺ from cytosol into SR/ER lumen.
How does SERCA cause muscle relaxation?
It lowers cytosolic Ca²⁺ by pumping Ca²⁺ back into the SR.
What distinguishes ABC transporters from P-type ATPases?
ABC transporters use ATP-binding domains without a phosphorylated Asp intermediate.
What is P-glycoprotein (ABCB1)?
An ATP-dependent ABC exporter that pumps many drugs out of cells.
How can P-glycoprotein contribute to multidrug resistance?
It exports drugs, reducing their intracellular accumulation.
Where is SGLT1 found in intestinal enterocytes?
On the apical membrane.
What does SGLT1 transport?
One glucose with two Na⁺ ions into the enterocyte.
Why is SGLT1 secondary active?
Downhill Na⁺ entry drives glucose uptake against its gradient.
What is GLUT2's role in intestinal glucose absorption?
Basolateral facilitated diffusion of glucose toward blood.
What is the overall sequence of intestinal glucose absorption?
Na⁺/K⁺ pump maintains Na⁺ gradient → SGLT1 imports glucose → GLUT2 exports glucose.
What is LacY?
A bacterial H⁺/lactose symporter.
What provides the energy for LacY transport?
The proton electrochemical gradient (proton-motive force).
What does ADME stand for?
Absorption, distribution, metabolism, and excretion.
What is the role of cytochrome P450 enzymes in pharmacology?
They metabolize drugs and influence clearance and drug interactions.
What is hERG (Kv11.1)?
A voltage-gated K⁺ channel important for cardiac repolarization.
What happens when a drug inhibits hERG?
Outward K⁺ current decreases, delaying ventricular repolarization.
What ECG change can result from hERG inhibition?
Prolongation of the QT interval.