MCAT topics → Nervous and Endocrine Systems → Resting Membrane Potential and Ion Gradients

Resting Membrane Potential and Ion Gradients

MCAT trap: Attributes resting potential directly to the Na+/K+ pump rather than to K+ leak channel diffusion. The resting membrane potential is primarily set by K+ leak channels (K+ diffusing out down its concentration gradient); the Na+/K+-ATPase maintains the gradients that make this possible but contributes only a small direct electrogenic effect.

Resting membrane potential is the baseline electrical state of a neuron at rest — approximately -70 mV — and the MCAT's most tested misconception on this topic is crediting the Na⁺/K⁺-ATPase with creating that potential. It does not. The pump maintains the ion gradients; K⁺ diffusing out through leak channels is what actually generates the -70 mV. The pump's direct electrogenic contribution is only a few millivolts. This distinction drives multiple MCAT question types: blocking the pump with ouabain causes only a slow drift, not an immediate collapse of potential.

The trickiest part is understanding the difference between what sets the resting potential versus what maintains it. Most students instinctively credit the Na+/K+-ATPase pump for creating the -70 mV, but that's wrong — the pump's direct electrogenic contribution is minor. The resting potential is dominated by K+ diffusing out through leak channels, which creates a charge separation. The pump's real job is to continuously restore the K+ and Na+ gradients that fuel that leak. If you blur this distinction, MCAT answer choices are written to exploit exactly that confusion.

A second common trap involves the Nernst equation. Students assume that because K+ is a cation (positive charge), its equilibrium potential must be positive. The opposite is true: EK is about -90 mV because K+ is concentrated inside and its net diffusion outward leaves the interior negative. The actual resting potential (-70 mV) is slightly less negative than EK because a small Na+ permeability at rest pulls the potential toward ENa (+60 mV). Understanding this balance — K+ leak dominates, Na+ leak perturbs slightly — is what separates students who truly understand this topic from those who just memorized the number.

Common misconceptions

Common mistake
Wrong: The Na+/K+-ATPase directly creates the resting membrane potential by pumping ions.
Right: The resting membrane potential is primarily set by K+ leak channels (K+ diffusing out down its concentration gradient); the Na+/K+-ATPase maintains the gradients that make this possible but contributes only a small direct electrogenic effect.
The Na+/K+-ATPase doesn't directly generate the -70 mV — it only maintains the ion gradients. The actual voltage is created when K+ diffuses out through leak channels down its concentration gradient, leaving behind impermeable anions and making the inside negative. Think of the pump as restocking the fuel; K+ diffusion through leak channels is the engine that actually generates the potential.
Common mistake
Wrong: The Na+/K+-ATPase pumps 2 Na+ out and 3 K+ in per ATP.
Right: The Na+/K+-ATPase pumps 3 Na+ out and 2 K+ in per ATP, making it electrogenic (net negative charge inside).
The stoichiometry is 3 Na+ out and 2 K+ in — not the reverse. This is a favorite MCAT trap because the numbers are easy to flip. The 3:2 ratio matters mechanistically: more positive charge leaves than enters, making the pump itself slightly electrogenic (contributes a few millivolts of negativity to the interior), though this effect is small compared to K+ leak.
Common mistake
Wrong: Na+ is the predominant intracellular cation at rest.
Right: K+ is the predominant intracellular cation at rest; Na+ is concentrated extracellularly.
K+ is the dominant intracellular cation — concentrations are roughly 140 mM inside vs. 5 mM outside. Na+ is the opposite: ~145 mM outside, ~12 mM inside. This asymmetry is actively maintained by the Na+/K+-ATPase. Flipping these distributions is a classic distractor; if you remember that the pump kicks Na+ out and pulls K+ in, the gradient directions follow logically.
Common mistake
Wrong: The Nernst equilibrium potential for K+ is positive because K+ is a positive ion.
Right: The Nernst equilibrium potential for K+ is approximately -90 mV (negative) because K+ is more concentrated inside and diffuses out, leaving net negative charge inside.
The sign of EK comes from the concentration gradient direction, not the charge of the ion. K+ is concentrated inside, so it diffuses outward, removing positive charge from the interior — this makes the inside negative. The Nernst equation for K+ yields approximately -90 mV. The fact that K+ carries positive charge is already accounted for in the equation through the valence term; what determines the sign is which side has higher concentration.
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What the exam tests

  1. Know the resting membrane potential value (~-70 mV) and what it means: the cell interior is negative relative to the extracellular fluid.
  2. Know which ion is concentrated where at rest: K+ is high inside, Na+ and Cl- are high outside, and the membrane at rest is much more permeable to K+ than to Na+.
  3. Understand the role of the Na+/K+-ATPase: it pumps 3 Na+ out and 2 K+ in per ATP, maintaining the gradients that K+ leak depends on, while contributing only a small direct electrogenic effect to resting potential.
  4. Explain why K+ leak channels — not the pump — are the primary determinant of resting membrane potential, and why the actual RMP is slightly less negative than the K+ equilibrium potential.
  5. Use the Nernst equation to calculate the equilibrium potential for K+ or Na+, and interpret what the sign and magnitude of that value mean physically.

Can you avoid these mistakes?

A researcher applies ouabain (a Na+/K+-ATPase blocker) to a neuron. In the first few seconds, membrane potential barely changes. Over the next several minutes, the resting potential gradually becomes less negative. Why does the potential stay stable initially but drift later — and which ion's movement is most responsible for the eventual depolarization?
The extracellular K+ concentration is experimentally raised from 5 mM to 20 mM. Using the logic of the Nernst equation (without necessarily calculating), predict whether the resting membrane potential becomes more negative, less negative, or stays the same, and explain why.
A student claims: 'The Na+/K+-ATPase is electrogenic, so it's the main source of the -70 mV resting potential.' Identify the error in this reasoning and explain what actually sets the resting potential and what role the pump genuinely plays.
For K+ (intracellular ~140 mM, extracellular ~5 mM), the Nernst potential is approximately -90 mV. The actual resting membrane potential is -70 mV. What does this discrepancy tell you about other ion permeabilities at rest, and which ion's leak is most responsible for the difference?

Related topics

Membrane Potential and the Nernst Equation Primary and Secondary Active Transport Neuron Structure (Dendrite, Axon, Myelin) Action Potential (Depolarization, Repolarization, Refractory Periods) Saltatory Conduction and Conduction Velocity Chemical and Electrical Synaptic Transmission

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