Questions: Selective Permeability and Membrane Channels

Question 1

The potassium channel achieves a selectivity ratio of 1,000:1 for K⁺ over Na⁺, even though Na⁺ is a smaller ion. What explains this counterintuitive result?

• A. Larger ions gain more momentum and pass through the pore more forcefully
• B. The selectivity filter carries a strong negative charge that attracts K⁺ but repels the smaller Na⁺
• C. The selectivity filter strips each ion's hydration shell; K⁺ is stabilized by precisely spaced carbonyl oxygens, while Na⁺ is too small to be stabilized and is therefore rejected
• D. Sodium channels exist in separate membrane domains inaccessible to K⁺

Answer: (C)

This is the key insight about channel selectivity: size is necessary but not sufficient. In solution, both K⁺ and Na⁺ are surrounded by hydration shells. To enter the selectivity filter, each ion must shed its water shell and be stabilized by carbonyl oxygens lining the pore. These oxygens are spaced perfectly for K⁺. Na⁺, being smaller, cannot be effectively stabilized — the energy cost of dehydration is not offset by the carbonyl interactions, so Na⁺ is excluded. The channel discriminates by chemistry and geometry, not just size.

Question 2

A student argues that ion channels are always ready to conduct because their pores are permanent open structures embedded in the membrane. What is wrong with this reasoning?

• A. Ion channels are not permanent structures — they are assembled in the cytoplasm and inserted only when needed
• B. Channels have gating mechanisms and are closed most of the time, opening only in response to specific signals such as voltage changes or ligand binding
• C. Ion channels do not allow passive movement — they actively use ATP to pump ions against their concentration gradients
• D. The student is correct; most ion channels are constitutively open structures

Answer: (B)

Channels are gated — they exist in open, closed, and inactivated states, and are closed the majority of the time. Voltage-gated channels open in response to membrane potential changes; ligand-gated channels open when a specific molecule binds. Option C confuses channels with pumps: channels are passive, exploiting existing concentration gradients without energy input. The gating property is essential for physiological control — a constitutively open sodium channel would depolarize neurons continuously and make signaling impossible.

Question 3

Ion channels act as pumps, using ATP to move ions against their electrochemical gradients and maintain the resting membrane potential.

• T. True
• F. False

Answer: False

Channels facilitate passive transport — they provide a low-resistance pathway for ions to move down their electrochemical gradient, requiring no energy input. The Na⁺/K⁺-ATPase pump (not a channel) uses ATP to move ions against their gradients and establish the resting potential. Channels then allow selective dissipation of that gradient for signaling. Confusing channels and pumps leads to fundamental errors about how membrane potential is established and how action potentials are generated.

Question 4

A voltage-gated sodium channel can enter an inactivated state — temporarily unresponsive — immediately after opening, due to an inactivation gate that swings shut even while the activation gate remains open.

• T. True
• F. False

Answer: True

This rapid inactivation is physiologically critical. After the activation gate opens in response to depolarization, a separate inactivation gate (the 'ball-and-chain' mechanism) swings into the pore within a fraction of a millisecond, blocking current even though the channel is technically 'open.' This inactivated state makes the channel temporarily refractory to re-opening and is responsible for the refractory period of the nerve impulse, ensuring action potentials propagate in one direction.

Question 5

Why is pore diameter alone insufficient to explain the selectivity of ion channels, and what additional factors determine which ions can pass?

Model answer: Pore diameter sets a size limit but cannot explain selectivity between ions of similar size, particularly cases where a larger ion is preferred over a smaller one. Selectivity also depends on how the ion interacts with the chemical environment of the selectivity filter. Ions in solution carry hydration shells; to pass through the narrowest region of the channel, they must shed this shell and be stabilized by residues lining the pore instead. The geometry and charge distribution of these residues determine whether a specific ion can be energetically stabilized — if not, the cost of dehydration exceeds the stabilization energy and the ion is rejected.

The potassium channel example makes this vivid: the pore is physically large enough for both K⁺ and Na⁺, but only K⁺ fits chemically. This principle generalizes — selectivity is always a function of size, charge, and hydration energetics together, not size alone.