Membrane potential is the difference in electrical charge between the inside and outside of a cell. In most cells at rest, the interior sits at roughly -70 to -80 millivolts (mV) relative to the outside, meaning the inside carries a net negative charge. This voltage exists because the cell membrane separates ions (charged particles) unevenly, much like a battery separates positive and negative plates.
How Cells Build an Electrical Charge
Every cell is wrapped in a thin lipid membrane that ions cannot freely cross. To move through, ions need specific protein channels or pumps embedded in that membrane. The key players are potassium (K+), sodium (Na+), and chloride (Cl-), each present at very different concentrations inside and outside the cell.
In a typical neuron, potassium is heavily concentrated inside the cell (about 125 mM) and scarce outside (about 5 mM). Sodium is the opposite: roughly 145 mM outside and only 15 mM inside. Chloride follows sodium’s pattern, sitting at about 150 mM outside and 13 mM inside. These steep concentration differences are the raw material for membrane potential.
At rest, the membrane is far more permeable to potassium than to anything else. Potassium naturally drifts outward through open channels, following its concentration gradient. As these positively charged ions leave, they strand negatively charged proteins inside the cell that are too large to follow. This separation of charge is what creates the voltage across the membrane. Potassium doesn’t escape indefinitely, though. As the inside becomes more negative, the electrical pull starts dragging potassium back in. Eventually the outward chemical push and the inward electrical pull balance, and a stable resting voltage forms.
The Sodium-Potassium Pump
Concentration gradients don’t maintain themselves. Left alone, the differences between inside and outside would gradually dissolve as ions leak across the membrane. Cells prevent this with an energy-hungry protein called the sodium-potassium pump, which uses one molecule of ATP to push 3 sodium ions out of the cell while pulling 2 potassium ions in. Because it moves more positive charges out than in, the pump itself adds a small negative bias to the interior.
More importantly, the pump continuously restores the concentration imbalances that make membrane potential possible in the first place. Without it, cells would lose their electrical charge within minutes and stop functioning.
Equilibrium Potentials for Each Ion
Each ion has its own “equilibrium potential,” the voltage at which that particular ion would stop moving across the membrane because the electrical and chemical forces on it are perfectly balanced. For potassium, this value is about -85 mV. For sodium, it’s about +60 mV. For chloride, it’s roughly -65 mV.
The resting membrane potential of a neuron (around -70 to -80 mV) sits very close to potassium’s equilibrium potential. That makes sense: at rest, the membrane is mostly permeable to potassium, so potassium dominates the voltage. Sodium’s equilibrium potential is far away in positive territory, which is why even a small increase in sodium permeability can shift the voltage dramatically, as happens during an action potential.
Scientists calculate membrane potential using an equation (the Goldman-Hodgkin-Katz equation) that weights each ion’s contribution by how permeable the membrane is to it at any given moment. At rest in the classic squid giant axon, the permeability ratio for potassium, sodium, and chloride is roughly 1 : 0.03 : 0.1. During an action potential, that ratio flips to 1 : 15 : 0.1, and sodium suddenly dominates the equation.
Action Potentials: Membrane Potential in Motion
The resting potential is not a fixed state. It’s a starting point. When a neuron receives a stimulus strong enough to push its voltage past a critical threshold (typically around -55 mV), voltage-gated sodium channels snap open. Sodium rushes into the cell, and the interior swings from negative toward positive territory, briefly approaching sodium’s equilibrium potential near +60 mV. This rapid swing is called depolarization.
Within a millisecond or so, those sodium channels close and potassium channels open wide. Potassium floods out, dragging the voltage back down past the resting level before the cell stabilizes again. This entire sequence, the action potential, is how neurons transmit signals along their length and communicate with other cells. It’s an all-or-nothing event: if the threshold is reached, the full spike fires. If not, nothing happens.
Why Membrane Potential Matters Beyond Neurons
Membrane potential isn’t just a neuron trick. Skeletal muscle cells use it to trigger contractions. Cardiac cells rely on carefully timed voltage changes to coordinate each heartbeat. Even non-excitable cells like those lining your gut use membrane potential to drive nutrient absorption: the voltage across the membrane helps pull glucose, amino acids, and other molecules into the cell through specialized transporters.
Cells also use hydrogen ion pumps to build steep gradients across internal membranes, which power everything from calcium signaling to the acidification of compartments that break down waste. In short, membrane potential is a universal energy source that cells tap for transport, signaling, and communication.
What Happens When Membrane Potential Goes Wrong
Diseases caused by defective ion channels, collectively called channelopathies, illustrate how critical membrane potential is. When the channels that control voltage don’t work properly, the consequences span nearly every organ system.
In the brain, mutations affecting sodium channels or receptors for the inhibitory signaling molecule GABA can make neurons too excitable, leading to epilepsy. Milder defects in one sodium channel subtype cause febrile seizures, while severe defects in the same channel cause Dravet syndrome, a serious childhood epilepsy. Different mutations in a single calcium channel gene can produce familial hemiplegic migraine, episodic ataxia, or a progressive movement disorder, depending on exactly how the channel is altered.
In the heart, channelopathies disrupt the precise timing of electrical signals that coordinate each beat. Long QT syndrome, short QT syndrome, and Brugada syndrome all stem from ion channel mutations that distort the cardiac action potential, raising the risk of dangerous arrhythmias. In one condition called catecholaminergic polymorphic ventricular tachycardia, a defective calcium release channel inside heart cells leaks calcium during each beat, triggering abnormal electrical activity that can cause sudden cardiac arrest during exercise or stress.
Outside the nervous and cardiovascular systems, cystic fibrosis is the most common genetic channelopathy in people of European descent, affecting roughly 1 in 2,500 live births. It results from a defective chloride channel, which disrupts the fluid balance on cell surfaces and leads to thick mucus buildup in the lungs. In skeletal muscle, loss of a chloride channel reduces the cell’s ability to restabilize after firing, causing the prolonged contractions characteristic of myotonia.
These examples underscore a simple point: membrane potential is not an abstract concept from a physiology textbook. It is the electrical foundation that keeps your neurons firing, your heart beating, and your cells transporting what they need to survive.