Conduction Physiology

Saltatory conduction: leaping the insulated cable

In an unmyelinated axon the action potential propagates continuously, each patch of membrane sequentially depolarizing its neighbour — a slow, metabolically expensive process limited to ~0.5–2 m/s. Myelination replaces this with saltatory conduction (Latin saltare, to leap): the high-resistance, low-capacitance sheath confines transmembrane current to the bare nodes of Ranvier, so the regenerative spike is excited only at successive nodes while the depolarizing current flows passively and almost instantaneously down the insulated internode between them. The action potential therefore appears to jump from node to node. The speed gain is enormous — large myelinated fibres reach 50–70 m/s — and it is purchased by the cable optimization described below.

The biophysical requirements are twofold. The internodal myelin must raise the membrane space constant λ enough that the passive voltage reaching the next node still exceeds threshold, and it must lower membrane capacitance so little charge is wasted swinging the internodal voltage. When both hold, current that would otherwise leak radially across the membrane is instead delivered longitudinally to the next node — conduction is fast because the current is not wasted.

Nodes of Ranvier: high channel density, high current

The node is a roughly 1 µm gap in the myelin where the regenerative machinery is concentrated. Its defining feature is an extraordinary density of voltage-gated Na⁺ channels (Nav1.6) — on the order of 1,000–2,000 channels/µm², orders of magnitude above the internodal axolemma. This concentration produces a large nodal inward current in a brief interval, generating enough charge to depolarize the next node to threshold across the intervening cable losses. The molecular architecture is precisely engineered: Na⁺ channels are anchored at the node by ankyrin-G and βIV-spectrin and fenced in by the paranodal junctions, while delayed-rectifier Kv1 channels sit in the juxtaparanode, shielded by myelin. In health the Kv channels are barely engaged; the nodal spike is dominated by fast Na⁺ entry, and conduction is efficient.

Determinants of conduction velocity and the 6 × diameter rule

For a myelinated fibre, conduction velocity scales linearly with total fibre diameter, and the relationship is captured by a remarkably durable empirical rule:

CV (m/s) ≈ 6 × fibre diameter (µm)

Thus a 12 µm fibre conducts at roughly 72 m/s and a 10 µm fibre at ~60 m/s — values that bracket the fastest motor and sensory axons sampled in routine studies. The linear scaling arises because larger diameter simultaneously lowers internal axoplasmic resistance (raising λ and speeding longitudinal current flow) and is accompanied by proportionally longer internodes and thicker myelin, so the leap distance per node grows in step with the cable improvement. (In unmyelinated fibres, by contrast, velocity scales only with the square root of diameter, which is why unmyelinated conduction is so much slower for a given size and why evolution favoured myelin for speed.) Two practical consequences follow. First, a clinically measured velocity reflects only the fastest-conducting fibres in the population, because the onset latency times the earliest arrivals; loss of the largest fibres slows the measured velocity even when most axons survive. Second, because velocity is set by diameter and myelin, it is the parameter that dissociates demyelinating from axonal pathology.

Temperature: the most common confounder in the laboratory

Cooling slows the gating kinetics of voltage-gated channels, prolonging the time course of the action potential at every node and therefore slowing propagation. The effect is large and quantifiable: conduction velocity falls by roughly 1.5–2.4 m/s for every 1 °C drop in limb temperature, and distal latencies lengthen by ~0.2 ms/°C. Cooling also increases amplitude and duration (slowed Na⁺ inactivation prolongs the spike and reduces phase cancellation), so a cold limb can mimic both demyelinating slowing and, paradoxically, healthier-looking amplitudes. Because the consequences are so systematic, temperature control is non-negotiable:

• Warm the limb to ≥ 32–34 °C at the recording site (some laboratories target ≥ 33 °C upper limb / ≥ 30 °C lower limb) and document the temperature.
• A cold limb is the most frequent benign cause of prolonged latencies, slowed velocities, and a falsely positive demyelinating picture — correct it before interpreting anything.
• Conversely, an unrecognized cold limb can mask a true conduction block by inflating distal amplitude; warming and repeating is the disambiguating maneuver.

Axon diameter, myelin integrity, and the collapse of the safety factor

The same physics that makes saltatory conduction fast makes it fragile. The margin by which nodal current exceeds the threshold demand of the next node is the safety factor, normally about 5–7×. Demyelination attacks this margin from two directions at once: stripping the internodal sheath raises capacitance (more charge is needed to swing the bared membrane) and lowers resistance (current leaks radially instead of reaching the next node). As the safety factor erodes, a graded spectrum of failure unfolds:

• Conduction slowing — the wavefront still reaches each node but later; internodal and nodal current is delivered more slowly, and velocity falls. This is the hallmark of demyelinating neuropathy and may include disproportionate prolongation of late responses and distal latencies.
• Temporal dispersion — different fibres slow by different amounts, so their potentials arrive desynchronized; the CMAP broadens, drops in amplitude, and becomes polyphasic through phase cancellation, even before any fibre blocks outright.
• Conduction block — once the depolarizing current can no longer bring the next node to threshold, the impulse fails to propagate across that segment. Demonstrating a focal drop in CMAP amplitude/area across a nerve segment, with preserved distal response, is the electrophysiological signature of focal demyelination and the basis for localizing entrapments and inflammatory lesions.

The critical lesion is the internode: failure of even a single internodal segment can drop conduction below the safety factor, which is why focal demyelination produces such disproportionate functional deficit relative to the small length of nerve involved. Newly demyelinated segments are also unusually temperature- and activity-sensitive — a marginally conducting fibre may block with mild warming, after exertion, or during high-frequency firing, explaining the fatigability and heat sensitivity (Uhthoff-type phenomena) characteristic of demyelinating disease.