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Differences in concentration of ions on opposite sides of a cellular membrane lead to a voltage called the membrane potential. Typical values of membrane potential are in the range –40 mV to –80 mV. Many ions have a concentration gradient across the membrane, including potassium (K+), which is at a high inside and a low concentration outside the membrane. Sodium (Na+) and chloride (Cl–) ions are at high concentrations in the extracellular region, and low concentrations in the intracellular regions. These concentration gradients provide the potential energy to drive the formation of the membrane potential. This voltage is established when the membrane has permeability to one or more ions. If the membrane is selectively permeable to potassium, these positively charged ions can diffuse down the concentration gradient to the outside of the cell, leaving behind uncompensated negative charges. This separation of charges is what causes the membrane potential.The system as a whole is electro-neutral. The "uncompensated" positive charges outside the cell, and the uncompensated negative charges inside the cell, physically line up on the membrane surface and attract each other across membrane. Thus, the membrane potential is physically located only in the immediate vicinity of the membrane. It is the separation of these charges across the membrane that is the basis of the membrane voltage. Other ions including sodium, chloride, calcium and others play a more minor role, even though they have strong concentration gradients, because they have more limited permeability than potassium.

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