Neural Action Potential — From Ions to Thought
Every thought, sensation, and movement begins with the same event: a brief electrical spike travelling along a neuron at up to 120 m/s. Understanding the action potential — its ionic basis, its all-or-nothing character, and its propagation — is the entry point to neuroscience.
1. Resting Membrane Potential
At rest, the inside of a neuron is about −70 mV relative to the outside. This is maintained by an unequal distribution of ions across the lipid bilayer membrane, which is impermeable except through selective ion channels.
| Ion | Inside (mM) | Outside (mM) | Ratio out/in |
|---|---|---|---|
| K⁺ (potassium) | 140 | 5 | 1:28 |
| Na⁺ (sodium) | 12 | 145 | 12:1 |
| Cl⁻ (chloride) | 4 | 120 | 30:1 |
| Ca²⁺ (calcium) | 0.0001 | 2 | 20 000:1 |
K⁺ tends to diffuse out (high inside → low outside) and Na⁺ tends to diffuse in. The Na⁺/K⁺-ATPase pump continuously maintains these gradients, pumping 3 Na⁺ out and 2 K⁺ in per ATP hydrolysed — consuming ~30% of the brain's energy budget at rest.
2. Nernst and Goldman Equations
The Nernst potential for an ion gives the membrane voltage at which electrical and diffusive forces balance (no net current for that ion alone):
R = 8.314 J/(mol·K) (gas constant)
T = 310 K (body temperature, ~37°C)
z = charge of ion (+1 for K⁺, +1 for Na⁺, −1 for Cl⁻)
F = 96 485 C/mol (Faraday constant)
E_K ≈ −90 mV (K⁺ Nernst potential)
E_Na ≈ +67 mV (Na⁺ Nernst potential)
E_Cl ≈ −70 mV (Cl⁻ Nernst potential)
The real resting potential (−70 mV) is a weighted average, captured by the Goldman-Hodgkin-Katz (GHK) voltage equation:
(P_K[K⁺]_i + P_Na[Na⁺]_i + P_Cl[Cl⁻]_o) )
P_X = membrane permeability to ion X
At rest: P_K : P_Na ≈ 25:1, so V_m ≈ E_K
3. Voltage-Gated Ion Channels
The action potential depends on two voltage-gated channels:
- Voltage-gated Na⁺ channel (Nav): Opens rapidly when membrane depolarises above threshold (~−55 mV). Has an activation gate (m) and an inactivation gate (h). Opens in ~0.1 ms, allows massive Na⁺ influx, then inactivates within 1 ms. Cannot reopen until the membrane repolarises (refractory period).
- Voltage-gated K⁺ channel (Kv): Opens more slowly on depolarisation. Allows K⁺ efflux, repolarising the membrane. No inactivation gate — closes simply when the membrane repolarises.
4. Phases of the Action Potential
Total duration: ~2 ms from threshold crossing to end of refractory period. Maximum firing rate limited to ~500 Hz.
5. Hodgkin-Huxley Model
Hodgkin and Huxley (Nobel 1963) described the action potential mathematically using voltage-clamp experiments on the squid giant axon. The model has 4 coupled ODEs:
dm/dt = α_m(V)(1−m) − β_m(V)·m (Na⁺ activation gate)
dh/dt = α_h(V)(1−h) − β_h(V)·h (Na⁺ inactivation gate)
dn/dt = α_n(V)(1−n) − β_n(V)·n (K⁺ activation gate)
Standard parameters: g_Na=120, g_K=36, g_L=0.3 mS/cm²
C = 1 µF/cm², E_Na=+55, E_K=−77, E_L=−54.4 mV
The α and β rate functions are exponential in V — empirically fitted to voltage-clamp data. The m³h product (activation cubed times inactivation) captures the rapid opening and delayed inactivation of the Na⁺ channel. See the Hodgkin-Huxley model article for simulation details.
6. All-or-Nothing Law
The action potential is all-or-nothing: a stimulus either fails to reach threshold (subthreshold: no AP) or, once threshold is crossed, the same full-amplitude spike is generated regardless of stimulus strength. There is no "medium" spike.
Information about stimulus intensity is encoded not in spike amplitude but in firing rate (rate coding) or spike timing (temporal coding). A stronger touch produces more rapidly firing mechanoreceptors, not larger spikes.
7. Propagation and Myelination
An action potential propagates because the current flowing into the depolarised membrane segment spreads to adjacent regions, raising their potential past threshold. Propagation is unidirectional because the already-activated region is in its refractory period.
In unmyelinated axons, conduction velocity scales with axon diameter: v ≈ 0.5–2 m/s for 1 µm diameter. In myelinated axons, the myelin sheath (Schwann cells / oligodendrocytes) insulates the axon, allowing current to jump between nodes of Ranvier — saltatory conduction:
Myelinated: v ≈ 6d m/s for d in µm
Example: 20 µm myelinated motor neuron → ~120 m/s
Example: 0.2 µm unmyelinated pain C-fibre → ~0.5 m/s
Multiple sclerosis destroys myelin — slowing or blocking conduction — explaining the varied neurological symptoms (vision loss, weakness, sensory disturbances) depending on which axons are demyelinated.
8. From Action Potential to Synapse
When an action potential reaches an axon terminal, it triggers synaptic transmission:
- The AP invades the terminal and opens voltage-gated Ca²⁺ channels.
- Ca²⁺ influx triggers exocytosis: synaptic vesicles fuse with the pre-synaptic membrane.
- Neurotransmitter (e.g. glutamate, GABA) diffuses across the 20 nm synaptic cleft.
- Neurotransmitter binds post-synaptic receptors — either ligand-gated ion channels (fast, ionotropic) or G-protein-coupled receptors (slow, metabotropic).
- Resulting post-synaptic potential (EPSP or IPSP) integrates with inputs from hundreds of other synapses at the dendrites and soma.
The human brain contains ~100 billion neurons and ~100 trillion synapses, each capable of transmitting ~1000 action potentials per second. The entire complexity of thought, memory, and consciousness emerges from this elegant piece of biophysics.