Source: Understanding Neural Signaling: Membrane Potentials & Synaptic Transmission
Tags: membrane potential, action potential, resting potential, ion gradient, voltage-gated channels, depolarisation, repolarisation, Na+/K+ pump, sodium-potassium pump, squid giant axon, Hodgkin and Huxley, myelin, saltatory conduction, nodes of Ranvier, all-or-none principle, threshold potential, electrochemical gradient
Neurons communicate using electrical signals driven by differences in ion concentrations across the cell membrane. A resting neuron sits at roughly −65 mV; when stimulated past a threshold, voltage-gated ion channels fire an all-or-none action potential that travels down the axon. Myelin speeds this process up dramatically through saltatory conduction.
Membrane potential (Vm)
The voltage difference between the inside and outside of a cell. In neurons, this voltage is the basis of all electrical signalling.
Resting membrane potential
The steady-state voltage of a neuron when it is not being stimulated, approximately −65 mV. The inside of the cell is more negative than the outside.
Ion gradient
The difference in concentration of a given ion (K+, Na+, Cl−) between the inside and outside of the cell. These gradients store the energy neurons use to generate electrical signals.
Na+/K+ pump (sodium-potassium ATPase)
An active transport protein that moves 3 Na+ ions out and 2 K+ ions in per cycle, using one ATP molecule. Maintains the concentration gradients that underpin the resting potential.
Ion channel
A membrane protein that allows specific ions to flow passively down their concentration gradient. Some are always open (leak channels); others are gated by voltage, ligands, or mechanical force.
Electrochemical gradient
The combined force acting on an ion, made up of its concentration gradient (chemical) and the membrane potential (electrical). Ions move down their electrochemical gradient when channels open.
Action potential
A rapid, transient reversal of the membrane potential that propagates along the axon. Triggered when depolarisation reaches threshold; follows an all-or-none pattern.
All-or-none principle
Once threshold is reached, the action potential fires at full amplitude every time. Below threshold, nothing fires. There is no partial action potential.
Threshold potential
The membrane voltage (typically around −55 mV) at which voltage-gated Na+ channels open in sufficient numbers to trigger a self-reinforcing depolarisation.
Depolarisation
A shift in membrane potential toward more positive values (e.g. from −65 mV toward 0 mV and beyond), caused by the influx of Na+ through voltage-gated channels.
Repolarisation
The return of membrane potential toward resting values after the peak of the action potential, driven by K+ efflux through voltage-gated K+ channels.
Myelin sheath
An insulating layer of lipid-rich membrane wrapped around axons by oligodendrocytes (in the CNS) or Schwann cells (in the PNS). Prevents ion leakage and enables saltatory conduction.
Saltatory conduction
The mode of action potential propagation in myelinated axons, where the signal "jumps" between nodes of Ranvier. Much faster and more energy-efficient than continuous conduction.
Nodes of Ranvier
Small gaps in the myelin sheath where voltage-gated ion channels are concentrated. Action potentials regenerate at these nodes during saltatory conduction.
At rest, K+ concentration is higher inside the neuron; Na+ and Cl− concentrations are higher outside.
K+ leak channels allow some K+ to diffuse out, making the interior more negative.
The Na+/K+ pump actively maintains these gradients by exporting 3 Na+ for every 2 K+ imported, at the cost of one ATP per cycle.
The balance between chemical driving force (concentration gradient pulling ions one way) and electrical driving force (charge difference pulling them the other way) establishes the resting potential at roughly −65 mV.
Channels allow passive movement down the electrochemical gradient. They are fast, selective, and can be gated (opened or closed) by voltage, ligand binding, or mechanical stretch.
Pumps use energy (ATP) to move ions against their gradients. They are slower but essential for resetting and maintaining the concentration differences that channels exploit.
A stimulus depolarises the membrane toward threshold (around −55 mV).
Voltage-gated Na+ channels open, and Na+ rushes in, driving rapid depolarisation toward +30 to +40 mV.
Na+ channels inactivate shortly after opening. Voltage-gated K+ channels open with a slight delay, and K+ flows out, causing repolarisation.
The membrane may briefly hyperpolarise (undershoot) before returning to resting potential.
The action potential propagates unidirectionally along the axon, like a chain of dominoes: each segment depolarises the next.
Alan Hodgkin and Andrew Huxley used the squid giant axon as their model because of its large diameter, which made electrical recording feasible.
Their work identified and characterised voltage-gated ion channels and produced a mathematical model of the action potential that remains foundational in neuroscience.
Oligodendrocytes (CNS) wrap axon segments in myelin, which insulates the membrane and prevents current leakage.
Between myelinated segments, nodes of Ranvier expose the axon membrane. Voltage-gated channels cluster at these nodes.
The action potential effectively jumps from node to node (saltatory conduction), greatly increasing speed and reducing metabolic cost.
Damage to myelin, as in multiple sclerosis, slows or blocks signal conduction. Symptoms vary depending on which axons are affected.
Nernst equation (single-ion equilibrium potential):
E_ion = (RT / zF) × ln([ion]_outside / [ion]_inside)
Where R = gas constant, T = temperature (K), z = ion valence, F = Faraday constant. This gives the voltage at which a particular ion's electrical and chemical driving forces balance.
Goldman equation (resting membrane potential, multiple ions):
Extends the Nernst equation to account for the relative permeability of the membrane to K+, Na+, and Cl− simultaneously. The resting potential sits closest to the equilibrium potential of whichever ion the membrane is most permeable to (at rest, that is K+).
⚠️ The resting potential is not zero. It sits at roughly −65 mV because K+ permeability dominates at rest.
⚠️ Channels are passive; pumps are active. Confusing the two is a common exam mistake.
⚠️ The all-or-none principle means action potential amplitude does not vary with stimulus strength. Intensity is coded by firing frequency, not spike size.
⚠️ Saltatory conduction is faster and more energy-efficient than continuous conduction. Expect questions linking myelin damage to conduction failure (e.g. multiple sclerosis).
⚠️ Hodgkin and Huxley's squid axon experiments are a classic exam reference. Know the model organism and what they discovered (voltage-gated ion channels, mathematical model of the action potential).
Q: What is the approximate resting membrane potential of a typical neuron, and why is the inside of the cell negative relative to the outside?
A: Approximately −65 mV. The inside is negative mainly because K+ leak channels allow K+ to diffuse out of the cell (down its concentration gradient), leaving behind unbalanced negative charges. The Na+/K+ pump reinforces this by exporting 3 Na+ for every 2 K+ it imports.
Q: Explain the all-or-none principle of action potentials.
A: Once the membrane reaches threshold (around −55 mV), voltage-gated Na+ channels open in a self-reinforcing cascade, and a full action potential fires. If the stimulus is below threshold, no action potential occurs. The amplitude of the action potential is always the same regardless of stimulus strength.
Q: How does saltatory conduction differ from continuous conduction, and why is it faster?
A: In continuous conduction, the action potential regenerates at every point along an unmyelinated axon. In saltatory conduction, myelin insulates the axon between nodes of Ranvier, so the depolarising current jumps from node to node. This skips the slow process of channel opening and closing along myelinated segments, increasing speed and reducing ATP consumption.
Q: What roles do ion channels and ion pumps play in maintaining the resting membrane potential?
A: Ion channels (especially K+ leak channels) allow passive ion flow down electrochemical gradients, which directly generates the resting voltage. Ion pumps (the Na+/K+ ATPase) use ATP to move ions against their gradients (3 Na+ out, 2 K+ in), maintaining the concentration differences that the channels rely on.
Q: Why was the squid giant axon important for Hodgkin and Huxley's research?
A: Its unusually large diameter (up to 1 mm) made it possible to insert electrodes and directly measure electrical activity across the membrane, which was not feasible in the smaller axons of most other organisms at the time.
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