The Membrane & Ions

The membrane is a phospholipid bilayer: two sheets of lipid with hydrophilic phosphate heads facing the watery fluids and hydrophobic fatty-acid tails buried in the core. That oily interior is the key to everything. To cross it, a substance must dissolve into an environment that is intensely water-hating.

Small, uncharged, non-polar molecules such as O₂ and CO₂ manage this easily and diffuse straight through. But an ion — Na⁺, K⁺, Cl⁻ — carries a fixed charge and a tightly bound shell of water molecules. Stripping that hydration shell to push the bare charge through an oily core costs an enormous amount of energy, so the rate of unaided crossing is effectively zero.

This is why the cell needs proteins. The bilayer sets the default — near-total impermeability to ions — and embedded proteins then punch through it to grant selective, controllable permeability. Channels provide water-filled pores that let specific ions flow down their gradients; pumps use energy to move ions against their gradients. Permeability is therefore not a property of the lipid but of which protein doors are present and open.

An ion that can cross the membrane is pushed by two independent forces, and you must handle both to reason correctly.

The chemical (concentration) gradient is the tendency of any substance to diffuse from where it is concentrated to where it is dilute. K⁺ is concentrated inside, so diffusion pushes K⁺ out.

The electrical gradient acts only on charged particles: an ion is pulled toward opposite charge and repelled by like charge. If the cell interior is negative, that negativity pulls positive ions (K⁺, Na⁺) in and pushes negative ions (Cl⁻) out.

Combine them and you get the electrochemical gradient — the net driving force on the ion. The two components can add together or oppose one another. For K⁺ at rest, the chemical force (outward) and the electrical force (inward) pull in opposite directions; the ion moves in whichever direction the stronger force wins. When the two exactly cancel, there is no net movement — a crucial idea for the next point.

At rest the fluids are strikingly unequal. K⁺ is high inside and low outside; Na⁺ and Cl⁻ are high outside and low inside; and there is a population of large impermeant anions — chiefly proteins, phosphates and other organic molecules — trapped inside because they are too big to cross and there are no doors for them.

These gradients are actively created. The Na⁺/K⁺-ATPase pump continuously exports Na⁺ and imports K⁺, building the steep Na⁺-out / K⁺-in arrangement. The fixed internal anions then shape the distribution of the permeant ions (a Gibbs–Donnan influence), helping draw Cl⁻ outward. The picture to hold: a K⁺-rich, protein-rich interior facing a Na⁺-rich, Cl⁻-rich exterior — an arrangement of stored potential energy the neuron will later spend on signalling.

Each permeant ion has an equilibrium potential — the membrane voltage at which its electrical and chemical forces exactly balance, so net flow stops. The Nernst equation calculates it from the ion's concentration ratio across the membrane. For the typical neuron, E_K ≈ −90 mV and E_Na ≈ +60 mV. Conceptually, E_K is the negative interior voltage strong enough to hold K⁺ in against its outward concentration gradient.

Now the decisive fact: at rest the membrane is far more permeable to K⁺ than to Na⁺, because many K⁺ leak channels are open while very few Na⁺ channels are. So the resting voltage is dominated by K⁺. Some K⁺ flows out down its gradient, each departing positive charge leaving the inside a little more negative, until the growing internal negativity nearly balances the outward push — pinning the voltage close to E_K.

But it does not reach E_K exactly. Because Na⁺ has a small but non-zero permeability, a trickle of Na⁺ leaks inward, carrying positive charge that makes the interior slightly less negative than −90 mV — hence roughly −70 mV. This is the Goldman (Goldman–Hodgkin–Katz) idea qualitatively: the resting potential is a weighted average of the equilibrium potentials of all permeant ions, each weighted by its permeability. K⁺ dominates the weighting, so V_m sits near E_K, nudged toward E_Na by the small Na⁺ leak (and Cl⁻ contributes too). Change a permeability and you slide V_m toward that ion's equilibrium potential — exactly what happens in an action potential.

The pump moves 3 Na⁺ out for every 2 K⁺ in, powered by one ATP. Because it exports one net positive charge per cycle, it is electrogenic and makes a small direct contribution to the resting potential — only a few millivolts of extra negativity.

Here is the classic distinction to state explicitly. What sets the resting potential right now is the selective permeability to K⁺ through the leak channels, which holds V_m near E_K. That is a permeability-and-diffusion phenomenon; it would still generate a negative voltage for a while even if the pump were switched off. What keeps the gradients topped up over time is the pump: every K⁺ that leaks out and every Na⁺ that leaks in slightly erodes the gradients, and the pump continuously restores them. Without it the gradients would run down over minutes to hours and the resting potential would eventually collapse — but the pump is the maintainer of the concentration gradients, not the moment-to-moment cause of the voltage. Getting this right is the single sharpest point in this topic.

Leak channels are effectively always open and set resting permeability. Gated channels open and close in response to a stimulus: voltage-gated channels respond to changes in membrane potential and drive the action potential (Topic 4); ligand-gated channels open when a neurotransmitter or other molecule binds, underlying synaptic potentials; and mechanically-gated channels open in response to physical stretch or pressure, as in touch and hearing receptors. The resting state is the quiet baseline; opening gated channels is how the neuron departs from it to signal.

"The pump directly causes the −70 mV." No — the pump's direct electrogenic contribution is only a few mV. The resting potential is set mainly by selective K⁺ permeability driving V_m toward E_K. The pump's essential role is maintaining the gradients that make that possible.

"At rest the membrane is impermeable to all ions." No — it is selectively permeable: highly permeable to K⁺ (open leak channels) and weakly permeable to Na⁺ and Cl⁻. The relative permeabilities, not zero permeability, produce the resting voltage.

"The resting potential equals E_K." No — it sits near E_K but is a few millivolts less negative because of the small Na⁺ (and Cl⁻) permeability. V_m equals E_K only in the hypothetical case of exclusive K⁺ permeability.

Serum potassium. Because the resting potential depends on the K⁺ gradient, changes in extracellular K⁺ shift it. In hyperkalemia, raised external K⁺ reduces the gradient, making E_K less negative and depolarising the resting membrane; this initially raises excitability but, if sustained, inactivates Na⁺ channels and impairs firing — dangerous for cardiac muscle. In hypokalemia, the membrane tends to hyperpolarise, reducing excitability. This is why potassium is monitored so carefully clinically.

Drugs and toxins on channels. Many agents act directly on channels. Local anaesthetics (e.g. lidocaine) block voltage-gated Na⁺ channels, preventing action potentials so pain signals never leave the region. Toxins such as tetrodotoxin (pufferfish) block Na⁺ channels and can paralyse, illustrating vividly that the ion channels underlying these gradients are the machinery of nervous function — and its vulnerabilities.