How Electrophysiology Works

Every neuron and muscle cell acts like a tiny battery, maintaining about -70 millivolts across its membrane when at rest. This resting potential exists because the cell actively pumps sodium ions out and potassium ions in using specialized protein pumps that consume energy. The result is a higher concentration of sodium outside the cell and potassium inside, creating both chemical and electrical gradients.

The cell membrane itself acts as an insulator, preventing ions from freely crossing. However, the membrane contains "leak channels" that allow some potassium to drift out along its concentration gradient, leaving behind negatively charged proteins that cannot escape. This leakage of positive charge outward contributes to the negative interior.

This polarized state is not passive—the cell constantly works to maintain it, spending roughly 20-40% of its energy budget on ion pumps. The voltage gradient creates potential energy, like water held behind a dam, ready to be released when the cell needs to generate an electrical signal.

When a stimulus reaches threshold (typically around -55 millivolts), voltage-sensitive sodium channels embedded in the membrane undergo a conformational change and pop open. Sodium ions, driven by both their concentration gradient and electrical attraction to the negative interior, flood into the cell at rates exceeding 10 million ions per second through each channel. This influx happens in less than a millisecond.

The rapid entry of positive sodium ions drives the membrane potential upward, not just to zero but overshooting to approximately +30 millivolts. At this peak, the inside of the cell is temporarily more positive than the outside—a complete reversal of the resting state. This explosive change is called an action potential and represents the fundamental unit of electrical signaling in the nervous system.

The sodium channels then automatically inactivate, slamming shut even while the membrane remains depolarized. Simultaneously, voltage-gated potassium channels open more slowly, allowing potassium to exit and restore negative charge to the interior. This repolarization brings the membrane potential back down, often briefly overshooting to become even more negative than rest before stabilizing.

An action potential doesn't stay in one spot—it moves down the axon like a falling row of dominoes. When one section of membrane depolarizes, the local electrical current spreads to adjacent regions, bringing neighboring patches of membrane to threshold and triggering their voltage-gated sodium channels to open. This creates a chain reaction that travels in one direction along the neuron's length.

In unmyelinated axons, this propagation occurs continuously but relatively slowly, around 0.5-2 meters per second. The signal must trigger every segment of membrane sequentially. However, many vertebrate neurons are wrapped in myelin, a fatty insulation produced by support cells that covers the axon except at small gaps called nodes of Ranvier.

In myelinated axons, the action potential "jumps" from node to node in a process called saltatory conduction. The myelin prevents ion flow through the covered membrane, so the electrical signal only needs to regenerate at the exposed nodes spaced about 1 millimeter apart. This jumping dramatically increases speed up to 120 meters per second while also saving energy since fewer ions need to be pumped back across the membrane.

When an action potential reaches the axon terminal, it encounters a specialized junction called a synapse—a narrow 20-40 nanometer gap between the sending neuron and its target. The electrical signal cannot jump this gap directly. Instead, depolarization opens voltage-gated calcium channels at the terminal, and calcium ions rush into the cell.

The influx of calcium triggers vesicles—tiny membrane-bound packages filled with neurotransmitter molecules—to fuse with the cell membrane and dump their contents into the synaptic cleft. A single action potential can release thousands of neurotransmitter molecules, which diffuse rapidly across the narrow gap. Common neurotransmitters include glutamate, GABA, dopamine, and serotonin, each with distinct effects.

These chemical messengers bind to receptor proteins on the receiving cell's membrane. Some receptors are ligand-gated ion channels that open immediately when neurotransmitter binds, allowing ions to flow and either depolarizing (excitatory) or hyperpolarizing (inhibitory) the target cell. Others activate slower chemical cascades inside the receiving cell. After transmission, neurotransmitters are either broken down by enzymes or pumped back into the sending cell for reuse.

A typical neuron receives input from hundreds to tens of thousands of other neurons, each forming synapses on its dendrites and cell body. Some of these inputs are excitatory, pushing the membrane potential toward threshold, while others are inhibitory, driving it further negative and making firing less likely. The neuron continuously integrates all these competing signals in both space and time.

Spatial summation occurs when multiple synaptic inputs arrive simultaneously at different locations on the neuron. The resulting voltage changes spread through the cell and combine at the axon hillock—a specialized region where action potentials initiate. Temporal summation happens when repeated signals arrive at the same synapse in rapid succession, with each input adding to the previous one before it decays.

If the combined effect of all inputs brings the axon hillock to threshold, an action potential fires and propagates down the axon. If not, the voltage changes simply dissipate. This integration process is how neurons perform computation—each cell acts like a tiny decision-making unit, weighing evidence from thousands of sources and producing an output only when the net input is sufficiently strong. This mechanism underlies everything from reflexes to reasoning.