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The resting membrane potential is the electrical voltage difference between the inside and outside of a neuron at rest, typically around negative 70 millivolts. The inside is more negative because potassium ions move out of the cell through open potassium leak channels, leaving behind negatively charged proteins. This charge separation creates the observed negative potential.

The sodium-potassium pump is a transmembrane protein that continuously moves three sodium ions out of the cell for every two potassium ions it pumps in, using cellular energy. This active transport creates concentration gradients with higher sodium outside and higher potassium inside the neuron, establishing the chemical driving force for ion movement.

At rest, potassium leak channels are the main type of ion channel that is open, allowing potassium ions to pass through the membrane. Most other ions cannot cross the lipid bilayer without help from transmembrane proteins because charged ions cannot diffuse through the hydrophobic interior of membranes.

Ion channels control which ions can cross the membrane and at what rate. Potassium leak channels allow potassium to diffuse down its concentration gradient out of the cell. This selective permeability, combined with the sodium-potassium pump's activity, maintains the charge separation that defines the role of ion channels in neuronal computation.

Potassium ions move out of the cell down their concentration gradient through open potassium leak channels. These positive charges leaving the cell, combined with negatively charged proteins remaining inside, cause the interior to become relatively more negative. Eventually, electrostatic repulsion balances outward diffusion, establishing the negative resting potential.

Tetrodotoxin, a neurotoxin from pufferfish, selectively blocks voltage-gated sodium channels and disrupts action potentials. However, it does not affect the resting membrane potential because the resting potential depends primarily on potassium movement, not sodium influx. This makes tetrodotoxin useful for silencing neuronal activity while preserving the resting state.

The resting membrane potential is the baseline electrical state of neurons. Changes in membrane potential from this resting level, such as during an action potential, form the basis for neural signaling and communication between neurons. Without a stable resting potential, neurons cannot generate or transmit electrical signals.