Neural Control and Coordination · Lesson 3 of 8
Resting Membrane Potential and Ionic Gradients
“The ion distribution, selective permeability, sodium–potassium pump and electrical meaning of a resting polarized membrane.”
• Define membrane potential and identify its sign at rest. • Explain the distributions of Na⁺, K⁺ and large anions across the axon membrane. • Describe how selective K⁺ permeability creates a negative resting interior. • State the 3 Na⁺ out / 2 K⁺ in transport ratio of the sodium–potassium pump. • Distinguish an ion concentration gradient from an electrical gradient.
How can a resting neuron hold electrical energy?
A neuron at rest looks quiet, but its plasma membrane is not electrically neutral in a local sense. The watery fluid inside and outside the cell contains dissolved ions, and a small separation of charge builds up along the two sides of the membrane. This creates a difference in electrical potential between the cell interior and the extracellular fluid. In many vertebrate neurons it is approximately −70 mV, although the actual value depends on the neuron type and conditions.
The electrical potential of the cell interior measured relative to the outside; negative values indicate a more negative interior.
The relatively stable membrane potential of an excitable cell when it is not generating an action potential.
A membrane is not a tiny battery filled with positively charged fluid outside and entirely negative fluid inside. The bulk fluids remain close to electrically neutral. Only a very small excess of charge accumulates near each membrane surface; because the membrane is extremely thin, that small separation is sufficient to create a measurable voltage. Understanding this resolves the apparent puzzle that a neuron can have a negative resting potential while still containing abundant positively charged potassium ions.
The composition of the inside differs from the outside
The axoplasm, or axonal cytoplasm, contains relatively high K⁺ and many large negatively charged proteins and other anions. Extracellular fluid contains relatively high Na⁺ and typically much less K⁺. An ion distribution is maintained through transport systems, selective permeability and the chemistry of the internal cell contents. The textbook focuses on Na⁺, K⁺ and large protein anions because they explain the principal polarity of an axon.
| Ion or solute | Relative level inside resting axon | Relative level outside | Important consequence |
|---|---|---|---|
| Na⁺ | Lower | Higher | Na⁺ has inward electrochemical driving force at typical rest |
| K⁺ | Higher | Lower | K⁺ tends to diffuse out through resting leak channels |
| Large protein anions | Mostly confined within cytoplasm | Relatively low for these species | Help determine charge balance and cannot freely cross membrane |
A chemical concentration gradient favours movement from higher concentration toward lower concentration. Thus K⁺ concentration favours outward diffusion, while Na⁺ concentration favours inward diffusion. But ions also respond to electrical forces: a negative interior attracts positively charged ions. The combination of concentration and voltage differences is the electrochemical gradient, and the two contributions can oppose or reinforce each other.
The combined effect of a solute's concentration difference and an electrical potential difference across a membrane.
Selective ion channels produce the resting potential
In a resting axon, K⁺ permeability is usually much greater than Na⁺ permeability. Potassium can move outward through open resting channels down its concentration gradient, leaving behind relatively less mobile negative charge. As the inside becomes more negative, the growing electrical attraction tends to pull K⁺ back inward. Outward chemical driving force and inward electrical force approach a balance, helping establish a stable negative membrane voltage.
Although the introductory text calls the resting membrane 'nearly impermeable' to Na⁺, this is a relative statement. Small Na⁺ leaks and other ion movements still occur. The resting potential is thus not necessarily equal to the exact equilibrium potential for K⁺; it depends on several permeabilities, ion gradients and background transport. It is appropriate to treat K⁺ as a major influence rather than the only ion involved.
The sodium–potassium pump maintains the gradients
A membrane protein that uses ATP to transport three Na⁺ ions out of the cell and two K⁺ ions in per transport cycle.
Over time, ion leaks would tend to reduce the unequal concentrations. The sodium–potassium pump counters this by spending ATP to move Na⁺ and K⁺ against their relevant electrochemical tendencies. In each cycle it exports 3 Na⁺ and imports 2 K⁺. This preserves the sodium-rich outside and potassium-rich inside needed for normal electrical excitability.
The pump is electrogenic because more positive charge leaves than enters in each cycle, and it contributes modestly to membrane voltage. However, the immediate rapid rise and fall of a normal action potential is generated primarily by changes in voltage-gated ion channel permeability, not by the pump suddenly switching direction. This distinction becomes essential when discussing depolarisation and repolarisation.
Visualise a polarized axonal membrane
Why calling the outside positive can be misleading
The source describes the outer surface of the membrane as positive and the inner surface as negative. That is a convenient visual shorthand. In quantitative physiology the membrane potential is defined as inside minus outside. Therefore an inside potential of −70 mV simply means the inner surface is at a lower potential relative to the reference outside. Both surrounding fluids contain positive and negative ions, so the labels do not claim that extracellular fluid contains only positive charge.
How a stimulus can change a resting potential
When neurotransmitters bind receptors or sensory channels respond to a physical stimulus, ion permeabilities may change locally. The resulting graded voltage changes can move the cell closer to or farther from the threshold for opening voltage-gated Na⁺ channels. At sufficient depolarisation, the regenerative action-potential mechanism can begin. A resting membrane is therefore ready to respond precisely because it maintains ion gradients and a potential difference.
Resting potential is not a completely fixed number: it may shift as cells receive inputs, extracellular K⁺ changes or channels open. What makes a neuron excitable is the availability of controlled ion channels that use the stored electrochemical gradients to transform an adequate stimulus into a propagating electrical event.
What happens if the pump is blocked for an extended period?
The immediate membrane voltage does not instantly disappear when the Na⁺/K⁺ pump is momentarily inhibited, because established gradients and leak channels persist for some time. However, continued leakage without active maintenance gradually dissipates ion differences. The neuron then becomes less able to generate consistent action potentials and may experience osmotic and other problems. The time course depends on cell type and metabolic state.
Problem
Inside an axon the K⁺ concentration is higher than outside. How can the inside still be negative?
- 1.K⁺ can diffuse outward through relatively abundant resting channels, leaving behind less mobile negative charges near the membrane.
- 2.This small charge separation creates a negative inside voltage even while many K⁺ ions remain inside.
- 3.Electrical force then opposes further K⁺ escape; the pump preserves the underlying concentrations.
Quick Quiz
Quiz
What does −70 mV mean for a resting axonal membrane?
Which ion has relatively high concentration inside a resting axon?
Which ion has a relatively high concentration outside?
Which permeability is usually larger in an unstimulated axon?
Which ratio describes the sodium–potassium pump?
Why does K⁺ efflux tend to make the axonal interior negative?
What creates the fast upstroke of an ordinary action potential?
Why are resting ion gradients maintained over time?
Practice Problems
- Explain the ionic basis of a typical resting membrane potential.
- Give the direction and energy source for the sodium–potassium pump.
- Why does a resting neuron have a potential difference if intracellular fluid is nearly electrically neutral?
- Compare concentration and electrical driving forces for K⁺ at rest.
- Predict the effect of prolonged failure of Na⁺/K⁺-ATPase.
High intracellular K⁺, low intracellular Na⁺, fixed internal anions and greater resting permeability to K⁺ cause some K⁺ efflux, leaving a negative interior near the membrane; electrical attraction opposes further loss. Other permeabilities contribute.
Key Takeaways
• Resting membrane potential is inside relative to outside and is usually negative in neurons. • At rest K⁺ is relatively high inside, while Na⁺ is relatively high outside. • K⁺ leak and selective permeability are major determinants of resting polarity. • Large intracellular anions are relatively immobile and contribute to ionic balance. • The Na⁺/K⁺ pump uses ATP to move 3 Na⁺ outward and 2 K⁺ inward per cycle. • The pump maintains long-term gradients; voltage-gated channels create rapid action-potential changes. • A small membrane-surface charge separation is enough to produce voltage while bulk fluids remain nearly neutral.