Transmembrane Potential vs. Nernst Equation- Are They the Same?

Two Terms, Two Different Things

People mix these up constantly. Transmembrane potential and the Nernst equation are related, but they are not the same thing. One is a measurable biological phenomenon. The other is a mathematical tool used to predict what that phenomenon should be under ideal conditions. Confusing them leads to bad experiments and worse conclusions.

This article cuts through the confusion. You'll understand what each term actually means, where they overlap, and where they diverge completely.

What Transmembrane Potential Actually Is

Transmembrane potential is the actual electrical voltage difference across a cell membrane at any given moment. It's measured in millivolts (mV). Every living cell with an intact membrane maintains one. Neurons use it for signaling. Heart cells use it for contraction. Your kidney cells use it to move water and ions around.

The resting membrane potential in most neurons sits around -70 mV. That negative value means the inside of the cell is electrically negative relative to the outside. This isn't some theoretical construct. You can stick an electrode into a neuron and measure it directly.

Real transmembrane potential is dynamic. It changes constantly based on:

• Ion channel open/close states
• ATP-dependent pumps moving ions against gradients
• External environment shifts
• Cell metabolic state

It's the sum total of every electrical and chemical force acting on the membrane right now. Not a prediction. The real thing.

What the Nernst Equation Actually Is

The Nernst equation is a formula that calculates the equilibrium potential for a single ion species across a membrane. That's it. That's all it does. It tells you what voltage would be needed to perfectly balance the chemical gradient for one specific ion.

Here's the equation:

E = (RT/zF) × ln([outside]/[inside])

Where:

• R = gas constant
• T = temperature in Kelvin
• z = ionic charge
• F = Faraday constant
• [outside]/[inside] = concentration ratio

At body temperature (37°C), this simplifies to approximately 61.5/z × log([outside]/[inside]) in millivolts.

The Nernst equation assumes a membrane that is perfectly selective for one ion. It ignores every other ion. It assumes no active transport. It assumes thermodynamic equilibrium. These assumptions are almost never true in real biology, but the equation is still useful as a baseline.

Where They Overlap

Here's where people get tangled up. The Nernst equation produces values that are expressed in the same units as transmembrane potential (millivolts). When you calculate the Nernst potential for potassium with typical intracellular and extracellular concentrations, you get roughly -90 to -95 mV. The actual resting potential of a neuron is around -70 mV.

So yes, the numbers look similar. But they're not measuring the same thing. One is what you calculate for potassium alone under ideal conditions. The other is what you actually measure when all ions, channels, and pumps are working together.

The Nernst potential for each major ion gives you reference points:

• Potassium: approximately -90 mV
• Sodium: approximately +60 to +70 mV
• Chloride: approximately -70 mV (varies widely)
• Calcium: approximately +120 mV (extremely concentration-dependent)

These values tell you which direction an ion will flow if a channel opens. If the membrane potential is -70 mV and potassium's Nernst potential is -90 mV, opening potassium channels will drive the membrane toward -90 mV. This is exactly what happens during hyperpolarization.

The Critical Differences

The Nernst equation calculates equilibrium. Real transmembrane potential rarely achieves equilibrium for all ions simultaneously. Your Na+/K+ ATPase pump continuously shuffles three sodium out and two potassium in. This maintains concentration gradients that would otherwise run down. The Nernst equation doesn't account for this pump at all.

Real membranes are never perfectly selective. A membrane might be 50 times more permeable to potassium than sodium, but it's not infinitely selective. The Goldman equation extends the Nernst logic to handle multiple ions with different permeabilities, but it's still just a calculation. Real cells have leak channels, voltage-gated channels, ligand-gated channels, and mechanically-gated channels all operating simultaneously.

Transmembrane potential is what you measure with an electrode. The Nernst equation is what you use to interpret what that measurement means for individual ion species.

Direct Comparison

When to Use Each One

Use transmembrane potential when you're doing experiments. Patch clamp recordings, microelectrode recordings, fluorescent dyes that report voltage—all of these measure transmembrane potential. If you're studying action potentials, synaptic currents, or any real-time electrical activity, you're working with transmembrane potential.

Use the Nernst equation when you need to interpret ion driving forces. Calculating whether a particular ion will flow into or out of a cell at a given membrane potential requires the Nernst potential as a reference. It's also essential for designing experiments with ion-selective electrodes and for understanding equilibrium potentials in textbooks.

The Goldman-Hodgkin-Katz (GHK) equation bridges some of this gap. It calculates membrane potential based on multiple ion concentrations and permeabilities. But it's still a calculation, not a measurement. Use it when you need a more realistic resting potential estimate than any single Nernst value provides.

How to Calculate the Nernst Potential

Here's how to actually do it with real numbers. Let's calculate the Nernst potential for potassium at 37°C.

Step 1: Gather your concentrations

Typical extracellular potassium: 4-5 mM. Typical intracellular potassium: 140-150 mM.

Step 2: Apply the simplified equation

E = 61.5 × log10([K+]_outside / [K+]_inside)

E = 61.5 × log10(5 / 145)

E = 61.5 × log10(0.0345)

E = 61.5 × (-1.46)

E = -89.8 mV

Step 3: Interpret the result

If the membrane potential is -70 mV and potassium's equilibrium is -90 mV, opening potassium channels will pull the membrane toward -90 mV. The driving force is the difference: 20 mV.

Calculate driving force for any ion like this:

Driving force (mV) = Membrane potential - Ion's Nernst potential

A positive driving force means the ion is being pushed into the cell. A negative driving force means it's being pushed out. The magnitude tells you how strongly the gradient is pulling.

The Bottom Line

Transmembrane potential is what exists. The Nernst equation is a tool for predicting what should exist for one ion under artificial conditions. They're not the same. Stop treating them as interchangeable.

Use the Nernst equation to understand ion behavior. Measure transmembrane potential to understand what's actually happening in your experiment. The equation gives you the map. The electrode tells you where you actually are.