MCAT topics → Cellular Assemblies and Membranes → Membrane Potential and the Nernst Equation

Membrane Potential and the Nernst Equation

MCAT trap: Attributes resting membrane potential to Na+ rather than to K+ leak channel permeability. The resting membrane potential is primarily set by K+ leak channels that make the membrane most permeable to K+ at rest, with Na/K-ATPase playing a secondary electrogenic role.

Membrane potential is the voltage difference across a cell membrane, and on the MCAT it's one of the most reliably tested topics in neuroscience. The resting value of -70 mV inside a neuron isn't arbitrary: it's dominated by K+ leak channels that make the membrane far more permeable to K+ than to anything else — not by the Na/K-ATPase pump, which is where most students go wrong first. The MCAT tests this concept across multiple angles — from the basic mechanism of resting potential, to plugging numbers into the Nernst equation, to interpreting what happens when ion concentrations shift in a passage.

The Nernst equation gives you the equilibrium potential for a single ion — the membrane voltage at which that ion has no net driving force. The Goldman equation extends this to a real membrane with multiple ions by weighting each ion's contribution by its permeability. These are conceptually distinct tools, and the MCAT will absolutely probe whether you know which one applies when. Students frequently confuse them, applying Nernst to the whole resting potential instead of using it as a single-ion tool.

The trickiest application questions involve changing extracellular ion concentrations and predicting which direction the membrane potential shifts. The logic here requires you to think about Nernst predictions, not just intuition — and intuition frequently gets it backwards for K+. If you've ever thought 'more K+ outside means more K+ leaves, so hyperpolarization,' you've made the most common mistake on this topic. Getting comfortable with the underlying gradient logic, not just the equation, is what separates correct answers from confident wrong ones on exam day.

Common misconceptions

Common mistake
Wrong: The resting membrane potential is primarily determined by Na+ because Na/K-ATPase actively pumps it.
Right: The resting membrane potential is primarily set by K+ leak channels that make the membrane most permeable to K+ at rest, with Na/K-ATPase playing a secondary electrogenic role.
The Na/K-ATPase does pump Na+ out and K+ in, but its direct electrogenic effect on membrane potential is small — it moves 3 Na+ out for every 2 K+ in, contributing only a few millivolts. What actually drives the resting potential to around -70 mV is the high K+ permeability through leak channels: K+ follows its concentration gradient out of the cell, leaving behind negative charges and generating a large inside-negative voltage. Think of the pump as maintaining the gradients, but the K+ leak channels as doing the heavy lifting for the actual potential.
Common mistake
Wrong: The Nernst equation calculates the membrane potential accounting for all ions simultaneously.
Right: The Nernst equation calculates the equilibrium potential for a single ion; the Goldman equation is needed to account for multiple ions with different permeabilities.
The Nernst equation is a single-ion tool. It tells you: 'If the membrane were only permeable to ion X, what voltage would balance X's concentration gradient?' That's the equilibrium potential for X, not the actual membrane potential. Real membranes are permeable to multiple ions simultaneously — that's where the Goldman equation comes in. Goldman weights each ion's Nernst potential by its relative permeability, so ions the membrane ignores (low permeability) barely influence the result, while dominant ions like K+ at rest pull the potential close to their Nernst value.
Common mistake
Wrong: Increasing extracellular K+ concentration hyperpolarizes the membrane by driving more K+ out of the cell.
Right: Increasing extracellular K+ reduces the outward K+ gradient, making the equilibrium potential less negative and depolarizing the membrane.
The intuition 'more K+ outside → more K+ leaves → hyperpolarization' is backwards. When extracellular K+ rises, the concentration gradient driving K+ out of the cell becomes smaller. The Nernst equation tells you directly: E_K = (RT/zF) × ln([K+]_out / [K+]_in). A higher [K+]_out makes this ratio larger, pushing E_K toward zero (less negative). The resting potential follows E_K upward — that's depolarization, not hyperpolarization. This is clinically relevant: hyperkalemia (high blood K+) depolarizes neurons and cardiac cells, which is why it's dangerous.
Common mistake
Gap: Missing that the Goldman equation weights ions by permeability, not just concentration
The Goldman equation extends the Nernst equation by weighting each ion's contribution by its relative membrane permeability, which is why Na+, K+, and Cl- are all included in calculating the actual resting potential.
The Goldman equation isn't just 'Nernst for multiple ions added together' — the key addition is permeability weighting. Each ion's concentration ratio gets multiplied by its relative membrane permeability (P_K, P_Na, P_Cl). At rest, P_K >> P_Na, so K+ dominates the Goldman result and the resting potential sits close to E_K (-90 mV), not E_Na (+60 mV). During an action potential, P_Na spikes, so Na+ terms dominate Goldman and the potential shoots toward E_Na. Understanding this weighting logic is what lets you predict how changes in channel activity — not just concentration — shift membrane potential.
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What the exam tests

  1. Explain why the resting membrane potential is dominated by K+ permeability through leak channels, and describe the secondary role of the Na/K-ATPase pump in setting that potential.
  2. Use the Nernst equation to calculate the equilibrium potential for a single ion (e.g., K+, Na+, or Cl-) given its intracellular and extracellular concentrations.
  3. Describe what the Goldman equation does differently from the Nernst equation — specifically, how it incorporates relative membrane permeabilities for multiple ions (Na+, K+, Cl-) to predict the actual resting membrane potential.
  4. Given a passage that changes extracellular ion concentrations, predict whether the membrane potential depolarizes or hyperpolarizes and explain the mechanism using equilibrium potential logic.

Can you avoid these mistakes?

The intracellular K+ concentration is 140 mM and extracellular K+ is 5 mM. Using the simplified Nernst equation (E = -61/z × log([X]_in/[X]_out) at 37°C), estimate the K+ equilibrium potential. Then explain why the actual resting membrane potential (-70 mV) is slightly more depolarized than this value.
A researcher replaces the extracellular solution with one that has K+ raised from 5 mM to 20 mM while keeping intracellular K+ constant at 140 mM. Predict whether the cell depolarizes or hyperpolarizes, and show the reasoning using the Nernst equation rather than intuition.
A passage describes a glial cell with high resting K+ permeability and negligible Na+ permeability. Would the Goldman equation predict a resting potential closer to E_K or E_Na for this cell? What would change if the cell suddenly expressed voltage-gated Na+ channels that opened at rest?
A student claims: 'The Na/K-ATPase is what creates the resting membrane potential because it's the one actively moving ions.' Identify what's correct in this statement, what's wrong, and explain the actual roles of the pump versus K+ leak channels in setting the resting potential.

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