One stimulus, one all-or-none answer
— and then a millisecond of silence.

The minimum high-yield framework

1. Excitable tissue — tissue that can generate and conduct an electrical impulse in response to a stimulus, by virtue of voltage-gated ion channels and a maintained resting potential. Nerve, skeletal, cardiac and smooth muscle, and some secretory cells.
2. Rest −70 mV, threshold −55 mV, peak +30 mV. Depolarisation of 10-15 mV takes the membrane from rest to threshold.
3. Upstroke is sodium. Not calcium. The voltage-gated Na⁺ channel has two gates: a fast activation (m) gate and a slow inactivation (h) gate.
4. Repolarisation is potassium, through delayed rectifier channels that open slowly and close slowly — which is why there is an after-hyperpolarisation.
5. All-or-none, and frequency-coded. Above threshold, amplitude is fixed. Stimulus intensity is signalled by firing frequency and by the number of fibres recruited.
6. Propagation is by local circuit current depolarising the membrane ahead. The refractory period behind prevents backward spread, so conduction is one-way.
7. Myelin gives saltatory conduction — the impulse regenerates only at nodes of Ranvier, where voltage-gated Na⁺ channels are concentrated. Faster, and metabolically cheaper.
8. Velocity rises with diameter, with myelination, with internodal length and with temperature.
9. Two classifications — Erlanger-Gasser (A with α β γ δ, B, C) for all fibres, Lloyd-Hunt (I-IV) for sensory fibres only.

The tissues are nerve, skeletal muscle, cardiac muscle, smooth muscle, and certain secretory cells including the pancreatic β cell and the adrenal chromaffin cell. Pacemaker cells are a specialised subset, not the definition — a recorded error is to answer “excitable tissue” with “pacemaker cells”.

Why it matters physiologically

The significance is that excitability converts a chemical or mechanical event into a signal that can travel a long distance without weakening. That single property supports:

• Rapid long-distance communication — a signal from the sole of the foot reaches the cord in tens of milliseconds without decrement.
• Muscle contraction — the action potential is the trigger for excitation-contraction coupling in skeletal, cardiac and smooth muscle.
• Homeostasis — every reflex arc, from the baroreceptor to the stretch reflex, depends on it.
• Sensation and the response to the environment — sensory transduction produces a graded receptor potential, and excitable tissue converts that into a propagated code.
• Secretion — depolarisation-triggered calcium entry drives exocytosis in nerve terminals and endocrine cells alike.

The two gates, and why they matter

The voltage-gated sodium channel has an activation (m) gate that is closed at rest and opens on depolarisation, and an inactivation (h) gate that is open at rest and closes on depolarisation. Both respond to the same signal; the m gate simply responds faster. That difference in kinetics is the whole mechanism:

1. At rest — m closed, h open. The channel is closed but available.
2. On reaching threshold — m opens quickly, h begins to close slowly. For a millisecond or so, both are open and sodium floods in.
3. Within about a millisecond — h closes. The channel is now closed and unavailable: no stimulus of any size can reopen it.
4. On repolarisation — m closes and h reopens, returning the channel to the resting, available state. Full recovery of the h gates takes 100 ms or more.

Two consequences follow, and both are worth stating explicitly in an answer. Because the channel must repolarise before h reopens, the action potential is self-limiting and cannot be sustained. And because inactivated channels cannot reopen, there is an absolute refractory period, which is what makes conduction unidirectional and caps the maximum firing frequency.

Previously examinedApril 2024 — excitable tissue defined, the development and propagation of the nerve action potential, and the determinants of conduction velocity. Worked answers in the library

The refractory period is also the mechanism of unidirectional propagation. Local circuit current spreads in both directions from an active patch of membrane, but the membrane behind is refractory and cannot respond, so only the membrane ahead fires. Conduction in the physiological direction is called orthodromic; conduction the other way, which can be produced experimentally by stimulating an axon in its middle, is antidromic. An antidromic impulse dies at the first synapse it meets, because synapses conduct one way only.

1. An active patch reverses its polarity. At the site of the action potential the inside of the membrane is transiently positive while the neighbouring resting membrane is still negative inside.
2. A local circuit flows. Positive charge moves along the axoplasm from the depolarised region toward the adjacent polarised region, and back along the outside — a complete current loop.
3. The adjacent membrane reaches threshold. That local current depolarises the membrane ahead; when it crosses threshold, voltage-gated sodium channels there open and a new, identical action potential is generated.
4. The process repeats, and only forwards. The membrane behind is in its absolute refractory period, so the backward limb of the current loop cannot fire it. The impulse therefore travels from one end of the axon to the other without decrement.

Notice what is not happening: nothing physical travels along the axon. Each action potential is a separate, locally generated event. The signal is a sequence of regenerations, which is precisely why it does not fade with distance the way a graded potential does.

Myelin is concentric wraps of glial plasma membrane — oligodendrocyte in the central nervous system, one cell contributing internodes to many axons; Schwann cell peripherally, one cell per internode. It is lipid-rich and therefore a good electrical insulator. Its two effects are:

• Membrane resistance rises. Current cannot leak out across the internode, so it runs down the axoplasm instead. λ rises.
• Membrane capacitance falls. Capacitance is inversely proportional to the separation of the two conducting surfaces, and myelin separates them by many membrane thicknesses. Less charge has to be moved to change the voltage, so τ falls and the membrane ahead reaches threshold sooner.

Between internodes lie the nodes of Ranvier, short bare segments carrying a very high density of voltage-gated sodium channels. Because current cannot cross the internode, the action potential can only be regenerated at a node, and it therefore appears to jump from node to node — saltatory conduction, from the Latin saltare, to leap.

Beyond speed there is a metabolic saving: sodium enters, and has to be pumped back out, only at the nodes rather than over the whole axonal surface. A myelinated fibre carries the same information for a fraction of the ATP.

Previously examinedOctober 2020 — the maintenance of the resting membrane potential, the two equations governing ion distribution, and the effect of extracellular potassium on excitability.

The resting membrane potential itself, and the Nernst and Goldman-Hodgkin-Katz equations that describe it, are taught in membrane potentials.

Differential blockade, in the order it happens

Local anaesthetic sensitivity broadly follows small-before-large, but myelination matters as much as size: small myelinated B fibres are blocked before smaller unmyelinated C fibres, because a myelinated fibre only needs three consecutive nodes exposed to fail, and those nodes are close together. The clinical order of onset in a neuraxial block is therefore:

1. B — preganglionic sympathetic. Blocked first; the sympathetic level is two or more segments higher than the sensory level.
2. C and Aδ — temperature, then pinprick. Cold sensation is lost before sharp sensation, which is why cold is the more sensitive bedside test of block height.
3. Aβ — touch and pressure. A patient can feel touch and pressure long after pinprick has gone. Telling them so before starting is what prevents the “I can feel that” conversation mid-incision.
4. Aα — motor and proprioception. Last to go, first to recover.

Local anaesthetic action, from the physiology

Local anaesthetics block the voltage-gated sodium channel from the axoplasmic side, binding preferentially to the open and inactivated states — use-dependent or phasic block, so a rapidly firing fibre is blocked faster. Because the drug must cross the axolemma in its unionised form and then act in its ionised form, the balance is set by pKa and tissue pH: the closer the pKa is to 7.4, the greater the unionised fraction at physiological pH and the faster the onset. That is why lidocaine (pKa around 7.9) is faster in onset than bupivacaine (pKa around 8.1), and why local anaesthetic is unreliable in infected, acidic tissue.

Hyperkalaemia at the nerve and the muscle membrane

A rise in extracellular potassium makes the resting potential less negative, which moves it toward threshold. The immediate effect is increased excitability. But a sustained depolarised resting potential holds the sodium channel inactivation gates closed, so as potassium rises further the tissue becomes inexcitable. That biphasic behaviour is why severe hyperkalaemia produces flaccid weakness and cardiac standstill rather than tetany, and it is the reason the direction of the potassium effect is so often stated backwards: it depends on how far the potassium has risen.

Nerve conduction studies and the compound action potential

A mixed peripheral nerve contains fibres of every class, so the extracellular record is the algebraic sum of thousands of all-or-none events — the compound action potential. With a subthreshold stimulus nothing fires. As stimulus strength rises, low-threshold (large) fibres fire first, and the recorded amplitude grows until a maximal stimulus excites every axon; beyond that, a supramaximal stimulus adds nothing. This is why neuromuscular monitoring uses a supramaximal stimulus: only then does a change in the recorded response mean a change at the junction rather than a change in how many fibres were stimulated.

The compound action potential also separates into peaks as it travels, because the faster classes outrun the slower ones — the A, B and C peaks that gave the classes their names.