Orris

resting membrane potential

Reading File
Finding Sources
Finding Sources
Reading File
Reading File
Reading File
Reading File
Reading File
Loading Image
Loading Image
Reading File
Here is a thorough explanation of the resting membrane potential, drawn from multiple physiology textbooks.

Resting Membrane Potential (RMP)

Definition

The resting membrane potential is the electrical potential difference that exists across the membrane of excitable cells (neurons, muscle) when they are not transmitting signals - i.e., between action potentials. By convention, the intracellular potential is referenced to the extracellular potential.
  • Neurons: approximately -65 to -70 mV (inside negative)
  • Skeletal muscle: approximately -90 mV
  • Cardiac muscle: approximately -85 to -95 mV
  • Erythrocytes: as low as -10 mV
The inside of the membrane is electrically negative relative to the outside.

Ion Concentrations Across the Membrane

The Na+/K+ ATPase pump establishes and maintains the following gradients (typical nerve fiber values):
IonExtracellularIntracellular
Na+142 mEq/L14 mEq/L
K+4 mEq/L140 mEq/L
  • Na+ is ~10x more concentrated outside
  • K+ is ~35x more concentrated inside

How the RMP Is Generated - Three Contributions

Na+-K+ pump and K+ leak channels diagram from Guyton & Hall
The Na+-K+ pump (left) and K+ "leak" channels (right). The selectivity filter allows K+ to exit the cell down its concentration gradient. - Guyton & Hall Textbook of Medical Physiology

1. Potassium Diffusion Potential (dominant factor)

At rest, the membrane is ~100x more permeable to K+ than to Na+, due to open K+ "leak" channels (tandem pore domain channels). K+ diffuses out of the cell down its steep concentration gradient (140 vs. 4 mEq/L). As K+ leaves, it takes positive charge with it, leaving behind large intracellular anions (proteins) that cannot cross the membrane. This creates a negative charge inside.
  • The Nernst potential for K+ = -94 mV (if K+ were the only ion)

2. Small Sodium Permeability (partially offsets K+ effect)

Na+ has a slight permeability through the same K+-Na+ leak channels, diffusing inward down its gradient (142 vs. 14 mEq/L). Na+'s Nernst potential = +61 mV. Because K+ permeability so greatly exceeds Na+ permeability, the Goldman equation gives a combined potential of -86 mV.

3. The Na+/K+ ATPase Pump (small direct electrogenic contribution)

The pump transports 3 Na+ out for every 2 K+ in, creating a net loss of positive charge from the cell interior. This electrogenicity adds an additional -4 mV, bringing the total to approximately -90 mV in a nerve fiber.
The pump's more important role is indirect: it maintains the concentration gradients for K+ and Na+ that drive the diffusion potentials above. Without it, the gradients would dissipate.
Three-panel diagram showing contributions to RMP from Guyton & Hall
Panel A: K+ diffusion alone = -94 mV. Panel B: K+ + Na+ diffusion = -86 mV. Panel C: Adding the electrogenic Na+/K+ pump gives ~-90 mV. - Guyton & Hall, Fig. 5.5

The Nernst Equation

The equilibrium potential for any single ion is given by the Nernst equation:
E_ion = (61 mV / z) × log([ion]_outside / [ion]_inside)
Where z = valence of the ion. This is the potential at which there is no net movement of that ion - the electrical gradient exactly balances the chemical (concentration) gradient.

The Goldman Equation

When multiple ions are permeable simultaneously, the Goldman (Goldman-Hodgkin-Katz) equation calculates the membrane potential by weighing each ion's Nernst potential by its relative permeability:
V_m = (61 mV) × log [ (P_K[K+]_out + P_Na[Na+]_out + P_Cl[Cl-]_in) / (P_K[K+]_in + P_Na[Na+]_in + P_Cl[Cl-]_out) ]
At rest, P_K >> P_Na, so the RMP is dominated by K+.
Alternatively, the chord conductance equation weights each ion's equilibrium potential by its relative conductance:
E_m = (G_K / G_T) × E_K + (G_Na / G_T) × E_Na + (G_Cl / G_T) × E_Cl + ...

Equilibrium Potentials (Summary)

IonEquilibrium Potential
K+~-94 mV
Na+~+61 mV
Cl-~-70 mV
Ca2+~+132 mV
The RMP of -70 mV sits close to E_K and E_Cl because those ions are most permeable at rest. It is far from E_Na and E_Ca2+.

Role of the Na+/K+ ATPase - Two Roles

  1. Direct electrogenic effect: pumps 3 Na+ out for every 2 K+ in, contributing ~-4 mV of negativity directly
  2. Indirect (dominant) role: maintains the K+ concentration gradient that produces the large K+ diffusion potential, and maintains the Na+ gradient that will later power the action potential upstroke

Equilibrium vs. Resting Potential

A cell at true electrochemical equilibrium for K+ would sit at -94 mV. The actual RMP is less negative (-70 to -90 mV) because:
  • Small inward Na+ leak constantly depolarizes the cell
  • The pump must continuously work to oppose this Na+ leak and restore gradients
This makes the resting state a steady state, not a true equilibrium.

Clinical Relevance

  • Hyperkalemia (high extracellular K+): reduces the K+ concentration gradient, shifts RMP toward 0 (depolarization). This can cause muscle weakness and fatal cardiac arrhythmias.
  • Hypokalemia (low extracellular K+): increases the gradient, hyperpolarizes the cell, making it harder to fire action potentials - also causing muscle weakness and arrhythmias.
  • Local anesthetics (e.g., lidocaine): block Na+ channels, preventing depolarization from the RMP to threshold.
Sources:
  • Costanzo Physiology, 7th Ed., pp. 25-27
  • Guyton & Hall Textbook of Medical Physiology, pp. 78-79
  • Neuroscience: Exploring the Brain, 5th Ed., pp. 282-287
This is a shared conversation. Sign in to Orris to start your own chat.