Membrane transport

Concept

Membrane transport

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Statement

Passive, facilitated and active movement across membranes.

Why it matters

fluid-mosaic-membrane established that the plasma membrane is a lipid bilayer studded with mobile proteins; membrane transport is the direct functional payoff of that architecture — the set of mechanisms by which a cell exploits its own selective permeability to control what crosses in and out. Everything else in this unit depends on it: signal-transduction and receptor-ligand-binding both begin with a signal engaging a transmembrane protein, and resting-membrane-potential is itself nothing more than membrane transport's ionic consequences viewed at electrical equilibrium.

Cells maintain steep concentration gradients — Na⁺, K⁺, Ca²⁺, H⁺, glucose — that underlie processes as different as nerve conduction, nutrient absorption and ATP synthesis; membrane transport is the machinery that both builds and spends those gradients.

Hypotheses

The lipid bilayer itself is essentially impermeable to ions and to most polar or charged solutes.Without this baseline impermeability there would be nothing for transport proteins to control — gradients would dissipate directly through the bilayer and the distinction between passive, facilitated and active transport would collapse, since every route would be equally uncontrolled. Transport proteins are saturable: each has a finite maximum turnover rate.A channel or carrier presents a finite number of binding or conduction events per second, so transport rate cannot rise indefinitely with concentration — it must plateau, exactly as in enzyme kinetics (michaelis-menten-kinetics). A carrier is a molecular machine with a catalytic cycle, not simply an adjustable hole. Primary active transport assumes a continuous supply of ATP (or, in a few transporters, light or an existing ion gradient) to repeatedly reset the transporter against its own concentration gradient; interrupt that supply and active transport collapses to passive leak on the timescale the pump's gradient itself decays.

Proof

J = -P\,A\,\Delta C

Passive diffusion of a small or nonpolar solute proceeds down its concentration gradient at a rate set by the permeability coefficient \(P\), membrane area \(A\), and the concentration difference \(\Delta C\); no protein or energy input is required, and the flux never saturates. A

v = \dfrac{V_{max}[S]}{K_t+[S]}

Facilitated diffusion still moves solute down its gradient, but through a channel or carrier protein; because the protein must bind solute and cycle through a limited number of conformations per second, rate saturates with a transport constant \(K_t\), exactly as in enzyme kinetics — unlike Step 1's unsaturating law. A

\Delta G_{transport} = RT\ln\!\left(\frac{C_{in}}{C_{out}}\right) + zF\Delta\psi

Moving a solute of valence \(z\) against its electrochemical gradient (resting-membrane-potential develops the \(\Delta\psi\) term fully) costs positive free energy. Primary active transport supplies this directly, coupling transport to ATP hydrolysis (\(\Delta G^{\circ\prime}\approx-30.5\,\text{kJ/mol}\)) — the Na⁺/K⁺-ATPase pumps 3 Na⁺ out and 2 K⁺ in per ATP hydrolysed. B

\Delta G_{total} = \Delta G_{solute} + \Delta G_{co\text{-}ion} \le 0

Secondary active transport moves a solute uphill without hydrolysing ATP itself, instead coupling that movement to a co-transported ion (usually Na⁺) moving down the gradient primary active transport already built; the coupled process's total free-energy change must remain negative overall, even though the solute's own term is positive. B

\text{Bulk transport: vesicle budding and fusion move cargo too large for any channel or carrier.}

For macromolecules and particles exceeding what a single protein pore could accommodate, the cell instead deforms a patch of membrane into a vesicle (endocytosis) or fuses one with the plasma membrane (exocytosis), bypassing Steps 1–4 entirely. A

Result

\Delta G_{transport}=RT\ln(C_{in}/C_{out})+zF\Delta\psi

Reading. Whether a solute needs a pump or moves for free is entirely a question of the sign of \(\Delta G_{transport}\): negative, and diffusion (passive or facilitated) suffices; positive, and only active transport, primary or secondary, can move it.

Scope. Applies to any solute crossing a semipermeable membrane; for charged solutes it requires knowing both the concentration ratio and the membrane potential, not concentration alone (Common errors).

Corollaries & converses

resting-membrane-potential is the special case of Step 3 at electrochemical equilibrium (\(\Delta G_{transport}=0\)), solved for \(\Delta\psi\) — that rearrangement is exactly the Nernst equation.
second-messengers signalling via Ca²⁺ exploits a steep electrochemical gradient maintained by continuous active transport, so that simply opening a channel produces a large, fast, reliable signal without any pump needing to act in real time.
Converse: if a solute is observed moving net against its own gradient, transport must be active, primary or secondary — passive or facilitated diffusion (Steps 1–2) can never, by Step 3, produce sustained net movement against \(\Delta G_{transport}>0\).

Fails without

Drop bilayer impermeability (Hypotheses): any polar solute would leak directly through the bilayer at a rate outside the cell's control, and the gradients nerve conduction and ATP synthesis depend on could never be established or held.
Cut the ATP supply to primary active transport: the Na⁺/K⁺-ATPase stalls, and the ion gradients it maintains decay via passive leak channels until Na⁺ and K⁺ approach equilibrium, collapsing resting-membrane-potential and, with it, every secondary active transporter that spends that gradient.

Common errors

Treating facilitated diffusion as "active" simply because it uses a protein — what determines active versus passive is the direction relative to the gradient and whether energy is directly coupled, not protein involvement.
Assuming all active transport hydrolyses ATP directly; secondary active transport spends an existing ion gradient instead (Step 4).
Using concentration alone to predict the direction of transport for a charged solute, ignoring the \(zF\Delta\psi\) term in Step 3.
Treating channels and carriers as interchangeable: channels are typically fast and effectively non-saturating over physiological concentrations, while carriers show clear Michaelis-Menten-like saturation (Step 2).

Discussion

The Na⁺/K⁺-ATPase was identified by Jens Skou in 1957, the first ion-transporting enzyme to be characterised; it typically consumes on the order of a third of a resting animal cell's ATP budget, an indication of how continuously active transport must run simply to hold the gradients other processes then spend.

Secondary active transporters are further divided into symporters, which move the driving ion and the solute in the same direction (e.g. the Na⁺-glucose cotransporter), and antiporters, which move them in opposite directions (e.g. the Na⁺/Ca²⁺ exchanger) — both spend the identical Na⁺ gradient, only the coupled geometry differs.

Common misconception: that active transport is simply "faster" than passive transport. Rate is set by transporter density and turnover number, not by the active/passive distinction; what active transport guarantees is direction (net movement against a gradient), not speed — a sparse pump can move solute far more slowly than an abundant open channel.

Worked examples

\text{Renal SGLT1: 2 Na}^+\text{ down-gradient couples to 1 glucose up-gradient}

Intestinal and renal epithelial cells reabsorb glucose against its own concentration gradient using SGLT1, a secondary active symporter: two Na⁺ ions moving down the steep electrochemical gradient the Na⁺/K⁺-ATPase maintains supply enough free energy (Step 4) to drag one glucose molecule uphill, even when intracellular glucose already exceeds the extracellular (luminal) concentration. A

\Delta G_{Na^+}\ (\text{2 ions, down-gradient}) \;+\; \Delta G_{glucose}\ (\text{1 molecule, up-gradient}) \le 0

Reading. No ATP is hydrolysed by SGLT1 itself; the energy is borrowed from the Na⁺ gradient that primary active transport elsewhere in the cell already paid for.

Scope. The identical coupled-transport logic underlies most nutrient and ion reabsorption in the gut and kidney.

Problems

A neuron's Na⁺/K⁺-ATPase is blocked by a drug. Predict, using Step 3 and the Fails without discussion, what happens to the resting membrane potential over the following minutes, and why.
Solution
With active transport stopped, Na⁺ and K⁺ continue to leak passively down their gradients through resting leak channels (Step 1's logic), but nothing resets those gradients. Na⁺ in and K⁺ out both proceed toward equalising intracellular and extracellular concentrations, so \(\Delta\psi\) drifts away from its normal resting value toward zero as the ionic asymmetry that sustains it is dissipated.
Explain, using Step 2, why a carrier-mediated glucose transporter (e.g. GLUT1) shows a maximum transport rate as extracellular glucose concentration rises, whereas simple diffusion of a lipid-soluble molecule across the same membrane does not.
Solution
GLUT1 must bind glucose and undergo a finite number of conformational cycles per second (Step 2); once every transporter is saturated with substrate, adding more glucose cannot increase throughput, giving the characteristic \(V_{max}\) plateau. A lipid-soluble molecule diffusing directly through the bilayer (Step 1) has no binding step and no finite cycling rate to saturate, so its flux keeps rising linearly with \(\Delta C\).
A solute is uncharged and its intracellular concentration is lower than extracellular. Using Step 3 with \(z=0\), determine the sign of \(\Delta G_{transport}\) for net inward movement, and state whether active transport is required.
Solution
With \(z=0\), the \(zF\Delta\psi\) term vanishes and \(\Delta G_{transport}=RT\ln(C_{in}/C_{out})\). Since \(C_{in}