Resting Membrane Potential (RMP)
The resting membrane potential (RMP) is the electrical voltage difference across the plasma membrane of an excitable cell (such as a neuron or muscle fiber) when it is at rest. This baseline electrical charge is negative on the inside of the cell relative to the outside. In a typical large neuron, this baseline value sits steadily at -70 mV.
The RMP is not a passive state; it is an active equilibrium that functions like a charged battery, storing potential energy to drive action potentials when the cell is stimulated.
The Two Primary Pillars of RMP
The resting potential is established and maintained by two major physiological factors: asymmetric ion distribution and selective membrane permeability.
1. Asymmetric Ion Concentrations (The Chemical Gradients)
Extracellular and intracellular fluids contain radically different combinations of electrolytes. Two specific cations dictate the membrane potential:
Potassium (K+): The dominant intracellular cation. Its concentration inside the cell is high (around 140 mEq/L) compared to outside (around 4 mEq/L).
Sodium (Na+): The dominant extracellular cation. Its concentration outside the cell is high (around 142 mEq/L) compared to inside (around 14 mEq/L).
2. Selective Membrane Permeability (Leak Channels)
At rest, the plasma membrane is not equally permeable to all ions. It contains a high density of non-gated K+ leak channels that remain open all the time.
The membrane is highly permeable to K+ at rest.
The membrane is virtually impermeable to Na+ at rest.
Because K+ leak channels are wide open, K+ ions continuously follow their chemical concentration gradient and diffuse out of the cell. As these positively charged ions exit, they leave behind trapped, large intracellular anions (like negatively charged proteins and organic phosphates) that cannot pass through the membrane. This loss of positive charge creates the net negativity inside the cell.
The Mathematical Framework: Nernst vs. Goldman
To quantify exactly how these ions create the voltage, biophysicists rely on two core equations, written here in standard keyboard text:
The Nernst Equation
The Nernst equation calculates the Equilibrium Potential (E) for a single isolated ion. This is the exact theoretical electrical force required to perfectly balance and counteract an ion’s chemical concentration gradient.
Formula: E = (RT / zF) * ln([Ion outside] / [Ion inside])
When simplified at normal body temperature (37 degrees Celsius), the equilibrium potentials for the individual core ions are:
Potassium Equilibrium Potential (E-K+): Approximately -94 mV (meaning if K+ were the only ion moving, the inside of the cell would drop to -94 mV).
Sodium Equilibrium Potential (E-Na+): Approximately +61 mV.
The Goldman-Hodgkin-Katz (GHK) Equation
Because the cell membrane is simultaneously exposed to multiple ions, the actual RMP is a combined balance calculated by the GHK equation. This formula takes into account both the concentrations and the relative permeabilities (P) of all major ions:
Formula: Vm = (RT / F) ln( (P-K[K+ out] + P-Na*[Na+ out] + P-Cl*[Cl- in]) / (P-K*[K+ in] + P-Na*[Na+ in] + P-Cl*[Cl- out]) )
Because the resting permeability to K+ is roughly 100 times greater than its permeability to Na+, the mathematical outcome pulls the final resting membrane potential close to the potassium equilibrium potential, resting safely at -70 mV instead of plunging all the way to -94 mV.
Maintenance: The Na+/K+-ATPase Pump
If K+ ions are constantly leaking out and Na+ ions are slowly trickling in, the concentration gradients would eventually flatten out, causing the RMP to collapse to 0 mV.
The Na+/K+-ATPase pump continuously counters this breakdown by utilizing ATP to force ions against their natural electrochemical gradients.
It pumps 3 Na+ ions OUT of the cell.
It pumps 2 K+ ions IN to the cell.
Because it exchanges 3 positive charges for only 2, it is inherently electrogenic, contributing a direct negative net charge of about -4 mV to -5 mV to the baseline potential. Its primary duty, however, is preserving the concentration differences that allow the passive leak channels to function.
Clinical and Tissue Variations
The exact resting membrane potential value varies significantly depending on the specific physiological requirements of different excitable tissues:
Large Neurons (-70 mV): This value balances high excitability with structural stability, allowing for rapid signaling along axons without accidental firing.
Skeletal Muscle (-90 mV): A deeper, highly negative baseline is required here to prevent involuntary muscle twitches or misfires.
Cardiac Ventricular Myocytes (-90 mV): Holds a highly stable, deep negative resting phase (Phase 4) to ensure the ventricles relax completely, allowing the chambers to fill fully with blood between beats.
Cardiac Pacemaker Cells (-55 mV to -60 mV): These cells lack a stable resting potential entirely. Their shallow baseline allows for spontaneous electrical decay, which drives the heart's natural automaticity.
Smooth Muscle Cells (-50 mV to -60 mV): A shallower baseline allows these tissues to sustain the slow, rhythmic, wave-like contractions needed in the gastrointestinal tract and blood vessels.
Resting Membrane Potential References
Hodgkin, A. L., & Horowicz, P. (1959). The influence of potassium and chloride ions on the membrane potential of single muscle fibres. The Journal of Physiology, 148(1), 127-160.
Post, R. L., Merritt, C. R., Kinsolving, C. R., & Albright, C. D. (1960). Membrane adenosine triphosphatase as a participant in the active transport of sodium and potassium in the human erythrocyte. Journal of Biological Chemistry, 235(6), 1796-1802.
Hall, J. E., & Hall, M. E. (2020). Guyton and Hall Textbook of Medical Physiology (14th ed.). Philadelphia: Elsevier.
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