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Human Physiology · Excitable tissues

The Resting Membrane Potential

Every cell carries a small voltage across its membrane. In nerve and muscle that voltage is the stored charge that each impulse spends. Understand where it comes from and you understand electrotherapy, fatigue and the danger of a high potassium.

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Part 2 · Excitable Tissues · Chapter 5 of 47

Learning objectives

By the end of this page you should be able to:

  • Define the resting membrane potential and state typical values for nerve and muscle.
  • Explain an equilibrium potential as a balance of chemical and electrical forces.
  • Use the Nernst equation to calculate equilibrium potentials for K⁺, Na⁺ and Cl⁻.
  • Explain, using the Goldman equation, why the resting potential sits close to the potassium equilibrium potential.
  • Describe the role of leak channels and the sodium–potassium pump.
  • Predict the effect of changes in plasma potassium, and link potassium shifts to exercise fatigue.

Why it matters

Nerves and muscles work by changing their membrane voltage quickly. Before you can understand that change, the action potential, you need the starting point.

That starting point matters in practice. Electrical stimulation works by pushing the membrane away from rest. A raised blood potassium shifts the resting voltage of every heart cell, which is why it can stop the heart. And the potassium that leaks from working muscle is one of the reasons it tires.

A voltage across the membrane

Place one electrode outside a cell and push a very fine one inside, and a voltmeter reads a steady negative value. That is the resting membrane potential. By convention the outside is zero, so the number describes the inside.

Figure 1 · A voltage across the membrane

The resting membrane potential as a separation of charge across the membrane A horizontal membrane with a thin layer of positive charges on its outer surface and negative charges on its inner surface. A voltmeter connected to a reference electrode outside and a microelectrode inside reads minus 70 millivolts. +−+−+−+−+−+−+−+−+−+−+−+−+−+−+−+−+−OUTSIDE — extracellular fluidINSIDE — cytoplasm−70 mVvoltmeterreference outside (0 mV)microelectrode insideA thin layer of charge on each face;the bulk fluids stay neutral
The inside is negative relative to the outside. The voltage comes from a tiny excess of charge held right at the membrane; the fluids on either side remain electrically neutral [1].

The voltage comes from a very small number of ions. A thin layer of extra positive charge sits on the outer face of the membrane and a matching layer of negative charge on the inner face. The fluids themselves stay neutral; only a tiny fraction of the ions present need to move to create the voltage [1].

CellTypical resting potential
Skeletal muscle fibreabout −90 mV
Ventricular heart muscleabout −90 mV
Neuronabout −70 mV
Smooth muscleabout −50 to −60 mV, often unstable
Red blood cellabout −10 mV

Equilibrium potentials

Imagine a membrane permeable only to potassium. Potassium is about 35 times more concentrated inside than outside, so it diffuses out through open channels. Each ion that leaves takes a positive charge with it, and the inside becomes negative.

That negativity pulls positive potassium back. Very soon the electrical pull inwards exactly balances the chemical push outwards. The voltage at which this happens is the equilibrium potential for potassium.

Figure 2 · Two forces on potassium

Chemical and electrical forces on potassium across a membrane with potassium leak channels Potassium is concentrated inside the cell at about 140 millimoles per litre and outside at about 4. Through leak channels, the concentration gradient pushes potassium out while the negative charge left behind pulls it back in. The two forces balance at about minus 95 millivolts. K⁺ leakchannelINSIDEOUTSIDEK⁺ about 140 mmol/LK⁺ about 4 mmol/LChemical forcepushes K⁺ outElectrical forcepulls K⁺ back inBalanced at about −95 mVthe K⁺ equilibrium potential
The equilibrium potential is where the two forces cancel. For potassium it is about −95 mV with typical concentrations.

The Nernst equation

The equilibrium potential for any single ion can be calculated from its concentrations on each side.

Nernst equation at body temperature

E (mV) ≈ (61.5 ÷ z) × log₁₀(concentration outside ÷ concentration inside), where z is the ion’s charge: +1 for Na⁺ and K⁺, −1 for Cl⁻.

IonOutside (mmol/L)Inside (mmol/L)Equilibrium potential
K⁺4140about −95 mV
Na⁺14212about +66 mV
Cl⁻1045about −81 mV

These are textbook concentrations; intracellular values vary between cell types, so the exact equilibrium potentials vary too. The pattern is what matters: potassium wants to take the membrane strongly negative, and sodium wants to take it strongly positive.

Figure 3 · Where the resting potential sits

Equilibrium potentials for potassium, chloride and sodium compared with resting membrane potentials A horizontal voltage scale from minus 110 to plus 80 millivolts. The potassium equilibrium potential is about minus 95, chloride about minus 81 and sodium about plus 66. Resting potentials of muscle, about minus 90, and neurons, about minus 70, sit close to the potassium value. -100-80-60-40-200+20+40+60+80Membrane potential (mV)K⁺ ≈ -95equilibrium potentialCl⁻ ≈ -81equilibrium potentialNa⁺ ≈ +66equilibrium potentialSkeletal and cardiac muscle about −90Typical neuron about −70Resting potentials sit close to EK,far from ENa — because at rest themembrane is far more permeable to K⁺.
The membrane potential is pulled towards the equilibrium potential of whichever ion it is most permeable to. Values calculated with the Nernst equation from typical concentrations [1].

Why rest sits near the potassium potential

A real membrane is permeable to several ions at once. Its voltage settles at a weighted average of their equilibrium potentials, and each ion’s weight is its permeability. Goldman worked out this relationship in 1943, now called the Goldman or constant-field equation [2].

At rest, many potassium leak channels are open, and very few sodium channels. Hodgkin and Katz estimated resting permeabilities in squid axon in the ratio potassium 1, chloride 0.45, sodium 0.04 [3].

Figure 4 · Permeability decides the voltage

Relative resting membrane permeability to potassium, chloride and sodium A horizontal bar chart of relative resting permeability: potassium 1, chloride 0.45, sodium 0.04, as estimated by Hodgkin and Katz in the squid giant axon. K⁺1Cl⁻0.45Na⁺0.04Relative resting permeability in squid giant axon (Hodgkin and Katz, 1949)Many potassium leak channels are open at rest; very few sodium channels are.
Potassium dominates at rest. These ratios, measured in squid axon, are the classic inputs to the Goldman equation [2, 3]. Values differ between cell types.

With potassium dominating, the resting potential lies close to the potassium equilibrium potential. The small sodium leak pulls it a little less negative. That is why a neuron rests at about −70 mV rather than −95 mV [1].

Hodgkin and Katz also showed that during an impulse the membrane’s sodium permeability rises enormously. The voltage then swings towards the sodium equilibrium potential [3]. Chapter 6 builds the action potential from exactly this idea.

The role of the pump

If ions leak continuously, why do the gradients not run down? Because the sodium–potassium pump from Chapter 3 keeps restoring them, moving three sodium out and two potassium in for each ATP.

The pump contributes only a few millivolts directly, because it moves more positive charge out than in. Its main contribution is indirect: it maintains the concentration gradients on which the whole resting potential depends [1, 5].

When energy fails, as in ischaemia, the pump slows. The gradients run down, the cell depolarises, and sodium and water accumulate inside, so the cell swells.

Changing the potassium outside

Because the resting potential follows the potassium gradient, changes in extracellular potassium have large effects.

Figure 5 · Raising outside potassium depolarises the cell

Calculated membrane potential against extracellular potassium concentration A graph with extracellular potassium on a logarithmic horizontal axis from 1 to 100 millimoles per litre and voltage on the vertical axis. A dashed line shows the potassium equilibrium potential; a solid curve shows the calculated membrane potential, which follows it at high potassium but flattens at low potassium. The normal range near 4 is shaded. -120-100-80-60-40-200124102050100normalK⁺ equilibrium potential (Nernst)Membrane potential(Goldman, PNa/PK = 0.04)Extracellular K⁺ (mmol/L, log scale)mV
More potassium outside, less negative inside. Curves calculated from the Nernst and Goldman equations with typical concentrations [1, 2]. During intense exercise, potassium around working fibres can more than double [4].
ConditionEffect on resting potentialWhat you may see
Hyperkalaemia (high plasma K⁺)Less negative (depolarised)Initially more excitable, then weakness as sodium channels inactivate; dangerous heart rhythms
Hypokalaemia (low plasma K⁺)More negative (hyperpolarised)Muscle weakness, cramps, abnormal heart rhythms
Intense exerciseLocal K⁺ rise around working fibres depolarises themContributes to fatigue [4]
IschaemiaPump failure lets gradients run downDepolarisation, cell swelling, loss of function

Each impulse in working muscle lets potassium out. Sejersted and Sjøgaard reviewed evidence that during high-intensity exercise, extracellular potassium can more than double [4]. The resulting depolarisation reduces excitability and may contribute substantially to fatigue in skeletal muscle [4].

The sodium–potassium pumps oppose this. Muscle can switch on its pumps within seconds of activity, and training increases how many pumps it has [5]. Part of what training improves is the muscle’s ability to keep its membrane potential under load.

Clinical relevance for the physiotherapist

  • Electrical stimulation. TENS and neuromuscular stimulation work by moving the membrane away from its resting potential towards threshold. Chapter 6 explains the threshold.
  • Potassium results. Patients with kidney failure, on certain diuretics, or after crush injury can have abnormal potassium. Check results before strenuous exercise and stop if the patient reports palpitations or new weakness.
  • Fatigue. Potassium shifts and pump capacity help explain why deconditioned patients fatigue quickly and why training improves endurance [4, 5].
  • Ischaemia and injury. Cells deprived of energy lose their resting potential; this is the cellular basis of conduction failure after nerve compression or reduced blood flow.

Assessment and application

SituationLink to this chapterAction
Renal patient starting exercisePlasma K⁺ sets resting potential of heart and muscleCheck latest potassium; monitor heart rate and rhythm symptoms
Patient on loop or thiazide diuretics with crampsPossible low potassiumReport to the medical team
Rapid fatigue in a deconditioned patientReduced pump capacity and K⁺ shiftsUse intervals with recovery; progress gradually
Planning electrical stimulationStimulus must move the membrane to thresholdSelect appropriate pulse duration and intensity (Chapter 6)

Practical skill · working out an equilibrium potential

For potassium with 4 mmol/L outside and 140 inside: 4 ÷ 140 = 0.029; log₁₀ of 0.029 is about −1.54; multiplied by 61.5 gives about −95 mV. Repeat with 8 mmol/L outside, as might happen around working muscle: the result is about −77 mV, a large depolarisation.

Common mistakes

  • Saying the pump produces the resting potential. It maintains the gradients; leak channels produce most of the voltage.
  • Thinking large numbers of ions move to create the voltage. Only a tiny fraction move.
  • Confusing the equilibrium potential of one ion with the membrane potential. The membrane potential is a weighted average.
  • Forgetting the sign convention: the value describes the inside relative to the outside.
  • Assuming hyperkalaemia always makes muscles more excitable. Prolonged depolarisation inactivates sodium channels and causes weakness.

Exam preparation

Long answer

Define the resting membrane potential. Explain its ionic basis, including the roles of ion gradients, permeability and the sodium–potassium pump.

  • Definition and typical values (table).
  • Ion gradients and equilibrium potentials; Nernst equation with a worked example (Figure 2, table) [1].
  • Permeability and the Goldman equation; why rest is near EK (Figures 3 and 4) [2, 3].
  • The pump: small direct contribution, essential indirect role [1, 5].
  • Applied: hyperkalaemia, hypokalaemia, exercise fatigue (Figure 5) [4].

Short notes

  • Nernst equation [1].
  • Goldman equation [2].
  • Leak channels and resting permeability [3].
  • Potassium shifts during exercise [4].

Viva and practical

  • “Why is the neuron resting potential not equal to EK?” — a small sodium leak pulls it less negative [1, 3].
  • “What happens to resting potential if extracellular potassium rises?” — it becomes less negative [1].
  • “Can exercise change potassium around muscle fibres?” — yes, it can more than double in intense exercise [4].
  • Practical: calculate EK for a given set of concentrations.

Current evidence

Exam and traditional teaching

The resting potential is presented as fixed, with plasma potassium constant and the pump a background housekeeping process.

What the evidence adds

In working muscle, potassium around the fibres changes substantially from moment to moment, and these shifts may contribute to fatigue [4].

Pump activity and pump numbers are actively regulated: switched on within seconds by activity, increased by training, and reduced by disuse and disease [5].

What the student should understand

The resting potential is set by gradients and permeability, as the exam answer says. In a working muscle it is also being defended continuously, and how well it is defended is something training can change.

Check yourself

10 questions on this page. Tap one to see the answer and the reasoning.

Q1. The resting membrane potential of a typical neuron is about:
  1. (A) +70 mV
  2. (B) 0 mV
  3. (C) −70 mV
  4. (D) −150 mV

Answer: (C) Inside negative, about −70 mV in neurons and about −90 mV in skeletal muscle [1].

Q2. The resting potential lies close to the potassium equilibrium potential because at rest:
  1. (A) The membrane is impermeable to potassium
  2. (B) The membrane is far more permeable to potassium than to sodium
  3. (C) Sodium channels are all open
  4. (D) The pump stops working

Answer: (B) The membrane potential is pulled towards the equilibrium potential of the most permeant ion [1, 2].

Q3. Using typical concentrations (K⁺ 140 inside, 4 outside), the potassium equilibrium potential is about:
  1. (A) +66 mV
  2. (B) −30 mV
  3. (C) −95 mV
  4. (D) −200 mV

Answer: (C) The Nernst equation gives about −95 mV for these concentrations [1].

Q4. The equation that predicts membrane potential from the concentrations and permeabilities of several ions is the:
  1. (A) Fick equation
  2. (B) Goldman (constant-field) equation
  3. (C) Starling equation
  4. (D) Henderson equation

Answer: (B) Goldman’s 1943 constant-field treatment gave good agreement with squid axon potentials [2].

Q5. Hodgkin and Katz estimated the resting permeability ratio PK : PNa : PCl in squid axon as about:
  1. (A) 1 : 1 : 1
  2. (B) 1 : 0.04 : 0.45
  3. (C) 0.04 : 1 : 0.45
  4. (D) 1 : 10 : 0

Answer: (B) Their 1949 measurements gave potassium dominance at rest, with sodium permeability rising sharply during activity [3].

Q6. What does the sodium–potassium pump contribute to the resting potential?
  1. (A) It creates almost all of the voltage directly
  2. (B) A small direct electrogenic part; its main role is maintaining the gradients
  3. (C) Nothing at all
  4. (D) It makes the inside positive

Answer: (B) Most of the voltage comes from leak through channels down gradients that the pump maintains [1, 5].

Q7. Raising extracellular potassium makes the resting membrane potential:
  1. (A) More negative
  2. (B) Less negative (depolarised)
  3. (C) Unchanged
  4. (D) Positive at any value above 5 mmol/L

Answer: (B) A smaller potassium gradient lowers the potassium equilibrium potential, so the cell depolarises [1, 4].

Q8. During high-intensity exercise, extracellular potassium around working muscle can:
  1. (A) Fall to zero
  2. (B) More than double
  3. (C) Stay exactly constant
  4. (D) Turn into sodium

Answer: (B) Sejersted and Sjøgaard describe shifts that can more than double extracellular potassium [4].

Q9. These potassium shifts are thought to contribute to:
  1. (A) Muscle hypertrophy
  2. (B) Fatigue, through reduced excitability
  3. (C) Bone growth
  4. (D) Improved coordination

Answer: (B) Depolarisation from raised potassium may reduce excitability and contribute substantially to fatigue [4].

Q10. Which change helps muscle cope with exercise-induced potassium shifts?
  1. (A) Fewer Na⁺–K⁺ pumps
  2. (B) More Na⁺–K⁺ pumps with training
  3. (C) Blocking all potassium channels
  4. (D) Lower sodium intake

Answer: (B) Training increases pump content; disuse and several chronic diseases reduce it [5].

Quick review

Key takeaways

  • The inside of a resting cell is negative: about −70 mV in neurons, −90 mV in muscle [1].
  • An equilibrium potential balances an ion’s chemical and electrical forces; the Nernst equation calculates it.
  • EK ≈ −95 mV, ENa ≈ +66 mV, ECl ≈ −81 mV with typical concentrations.
  • The membrane potential is a permeability-weighted average (Goldman). At rest potassium dominates, so rest is near EK [2, 3].
  • The pump maintains the gradients; its direct electrical contribution is small [1, 5].
  • Raised extracellular K⁺ depolarises. In intense exercise it can more than double around muscle fibres, contributing to fatigue [4].

Further reading

SourceWhy it earns its place
Wright SH — Advances in Physiology Education, 2004A short, clear refresher written for students [1]
Hall JE, Hall ME — Guyton and Hall Textbook of Medical PhysiologyStandard account of membrane potentials
Kandel ER et al. — Principles of Neural ScienceThe neuroscience view of membrane potentials
Sejersted OM, Sjøgaard G — Physiological Reviews, 2000Potassium shifts in exercising muscle and heart [4]

References

  1. Wright SH. Generation of resting membrane potential. Advances in Physiology Education. 2004 Dec;28(1–4):139–142. doi:10.1152/advan.00029.2004 PMID 15545342 Teaching review
  2. Goldman DE. Potential, impedance, and rectification in membranes. Journal of General Physiology. 1943 Sep 20;27(1):37–60. doi:10.1085/jgp.27.1.37 PMID 19873371 Original theory
  3. Hodgkin AL, Katz B. The effect of sodium ions on the electrical activity of giant axon of the squid. Journal of Physiology. 1949 Mar 1;108(1):37–77. doi:10.1113/jphysiol.1949.sp004310 PMID 18128147 Experimental study
  4. Sejersted OM, Sjøgaard G. Dynamics and consequences of potassium shifts in skeletal muscle and heart during exercise. Physiological Reviews. 2000 Oct;80(4):1411–1481. doi:10.1152/physrev.2000.80.4.1411 PMID 11015618 Review
  5. Clausen T. Na+-K+ pump regulation and skeletal muscle contractility. Physiological Reviews. 2003 Oct;83(4):1269–1324. doi:10.1152/physrev.00011.2003 PMID 14506306 Review

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