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The resting membrane potential is the electrical potential difference between the inside and outside of a neuron at rest, typically around negative 70 millivolts. The inside is more negative because positive potassium ions move out of the cell through open potassium channels, while negatively charged proteins remain trapped inside, creating a polarized state essential for neural signaling.

The sodium-potassium pump is a transmembrane protein that continuously pumps three sodium ions out of the cell for every two potassium ions pumped in. This active transport process uses energy to create concentration gradients, establishing higher sodium concentrations outside the neuron and higher potassium concentrations inside, which drives the resting membrane potential.

At rest, potassium channels are the main type of ion channel open in the neuron membrane. Most ions cannot passively diffuse through the lipid bilayer because charged ions cannot cross its hydrophobic interior. Potassium channels allow potassium ions to move down their concentration gradient, making the resting membrane potential primarily determined by potassium movement.

Negatively charged proteins are trapped inside the neuron and cannot cross the cell membrane. Combined with the outward movement of positive potassium ions, these internal negative charges create the relative negativity inside the membrane. This accumulation of negative charge inside contributes directly to the negative resting potential of approximately negative 70 millivolts.

Tetrodotoxin is a neurotoxin that selectively blocks voltage-gated sodium channels, preventing sodium ions from entering the cell. However, it does not disrupt the resting membrane potential because the resting state depends primarily on potassium permeability and the sodium-potassium pump, not sodium channel activity. It disrupts action potentials instead.

As potassium ions diffuse out of the cell, positive charges accumulate outside the membrane, creating electrostatic repulsion that opposes further outward movement. Eventually, outward diffusion of potassium is balanced by this electrostatic repulsion, reaching electrochemical equilibrium. This balance produces the stable negative resting potential observed in neurons.

The resting membrane potential is measured by inserting a microelectrode into a neuron and comparing the electrical charge to a reference electrode in the extracellular fluid. This technique reveals the voltage difference between the inside and outside of the cell membrane, typically showing a negative value around negative 70 millivolts in resting neurons.