2.2 Action Potential Phases, All-or-None Response, and Refractory Periods

2.2 Action Potential Phases, All-or-None Response, and Refractory Periods

From rest to a regenerative spike

An action potential (AP) is a brief, stereotyped reversal of membrane voltage that travels along the axon. It starts only if a stimulus drives the membrane to threshold — typically near −55 to −50 mV in teaching diagrams, a few tens of millivolts positive to rest. Below threshold, voltage-gated Na+ current is too small to overcome K+ leak and outward K+ current; the membrane returns electrotonically (passively) toward rest. At threshold, Na+ current becomes regenerative: depolarization opens more voltage-gated sodium channels, more Na+ enters, further depolarization opens still more channels. That positive feedback is the upstroke.

Think of threshold as a current-balance point, not a millivolt stamped on the stimulator. When inward Na+ current exceeds outward currents, the voltage runs away toward ENa. When it does not, leak and K+ currents win and nothing propagates. That binary outcome at the single-axon level is the physiologic meaning of all-or-none.

All-or-none in one axon, graded in the compound recording

All-or-none means a single axon either fires a full AP or it does not. You do not get a half-sized spike by giving a half-threshold shock to that axon. Suprathreshold stimuli do not make that axon's spike much taller; they may shorten latency slightly or, far more importantly in the lab, recruit neighboring axons.

The compound muscle action potential (CMAP) and sensory nerve action potential (SNAP) on the screen are not all-or-none. Their amplitudes grow as you raise stimulus intensity because you recruit more axons, each contributing its own all-or-none extracellular field. Maximal stimulation is the intensity that has recruited essentially all available axons of that nerve (plus a small safety margin). A small CMAP after a truly supramaximal stimulus means fewer muscle fibers depolarized — axonal loss, conduction block between stimulus and recording sites, or a neuromuscular/muscle problem — not that each remaining axon fired a miniature AP.

This distinction prevents a common interpretation error. Growing SNAP amplitude during an intensity ramp is a recruitment curve, not evidence that individual sensory axons have graded spike heights. Flattening of that curve at high milliamps means you have run out of recruitable large fibers, not that the membrane abandoned all-or-none physiology.

Phases of the axonal action potential

Walk the intracellular voltage as a sequence. Rest is K+ leak. A depolarizing stimulus moves voltage toward threshold. If threshold is crossed, Na+ activation gates open rapidly. Na+ rushes in down both its chemical gradient and the electrical gradient (the interior is still negative early in the upstroke). Intracellular voltage races through 0 mV and overshoots toward ENa, often to about +30 to +40 mV in teaching traces. Almost immediately, Na+ inactivation gates close on a millisecond scale and voltage-gated K+ channels open. K+ leaves; interior voltage falls: repolarization. While K+ conductance is still high, voltage can dip negative to rest: afterhyperpolarization (undershoot), because the membrane is briefly even more K+-selective and is pulled toward EK. Then K+ channels close, Na+ channels recover from inactivation, and leak physics restores RMP.

Depolarization in AP language means the upstroke driven by voltage-gated Na+ influx. Do not confuse that with the slow, small depolarization a subthreshold shock produces. Repolarization is restoration of interior negativity: Na+ channels inactivate and K+ leaves through voltage-gated K+ channels. Hyperpolarization / afterhyperpolarization is the undershoot below RMP while K+ conductance remains high.

Exam trap: attributing the upstroke to the Na+/K+ pump. The pump is far too slow to make a 1-millisecond spike. The upstroke is channel current. Another trap: thinking K+ influx causes depolarization. K+ efflux repolarizes; Na+ influx depolarizes. A third trap: calling the overshoot "the CMAP." The overshoot is an intracellular millisecond event in one axon; the CMAP is a summed extracellular muscle field lasting many milliseconds.

Voltage-gated Na+ channels have two functionally separate gates in the usual teaching model. The activation gate opens quickly with depolarization (permits the upstroke). The inactivation gate closes more slowly with depolarization (stops Na+ current even though the membrane is still positive). Recovery from inactivation requires repolarization. That recovery requirement is the molecular reason for refractory periods.

Threshold and the strength-duration idea

Threshold is not a magic millivolt printed on the stimulator. It is the voltage at which inward Na+ current exceeds outward currents. Local factors shift it: membrane excitability, temperature, ischemia, and how abruptly you depolarize.

Stimulators deliver extracellular current. Whether that current brings axons to threshold depends on intensity and pulse duration. The strength-duration relationship says a long pulse can reach threshold with less current than a very short pulse. Rheobase is the minimal current that still works if the pulse is made very long. Chronaxie is the duration needed at twice rheobase — a teaching index of excitability. You do not need to calculate chronaxie during a routine nerve conduction study (NCS), but you should understand why a 0.1 ms pulse may need higher milliamps than a 0.2 or 0.5 ms pulse to recruit the same axons, and why extremely brief pulses can fail to depolarize despite a high indicated current.

Cathodal stimulation depolarizes axonal membrane under the cathode (negative pole) by making the outside locally more negative, which is equivalent to depolarizing the transmembrane voltage. That is why cathode placement relative to the recording site is a practical rule sitting on this physiology, not a superstition.

Absolute and relative refractory periods

After an AP, Na+ channels are inactivated and cannot immediately reopen. During the absolute refractory period, no stimulus, however strong, elicits another AP in that axon. This interval spans the upstroke and most of repolarization. It sets a hard ceiling on firing frequency: if the spike and absolute refractory period occupy roughly 1–2 ms, theoretical maximum rates are hundreds of hertz, but real axons and neuromuscular systems rarely use that ceiling.

During the relative refractory period, some Na+ channels have recovered, yet K+ conductance may still be high and remaining Na+ availability is reduced. A stronger-than-normal stimulus can elicit an AP, often with a slower upstroke and, in isolated-axon teaching, a lower safety factor. Afterhyperpolarization contributes to this reduced excitability by holding voltage farther from threshold.

Why this matters on NCS: very high stimulus rates (repetitive nerve stimulation, paired shocks, or an inadvertent double pulse) can fall into refractory periods. The second shock may elicit a smaller response or none in axons still recovering. That is a membrane-recovery limit, not proof that the stimulator failed electrically. F-waves and H-reflexes also live with refractory constraints; the core idea here is enough: refractory membrane cannot be treated as a rest-ready recruitable axon.

Worked scenario: why a subthreshold stimulus produces no SNAP

Setup. You place ring electrodes on digit 3 and stimulate the median nerve at the wrist, intending an orthodromic SNAP. Intensity is 4 mA at 0.1 ms. The screen shows stimulus artifact and a flat baseline. You raise intensity to 12 mA and a SNAP appears.

Why the first trial was silent. The 4 mA pulse depolarized nearby membranes a few millivolts but did not bring a recordable population of sensory axons to threshold. Without regenerative Na+ influx, those axons produced no propagating APs. No traveling AP volley means no summed extracellular SNAP at the rings. You might still see artifact (stimulus current spreading into the recording montage). Artifact is current from the stimulator, not a SNAP.

Could a tiny SNAP exist from tiny APs? Not from subthreshold axons. All-or-none says those axons contributed zero spikes. A very small SNAP, when one appears just above threshold, means few axons reached threshold, not that many axons fired miniature spikes. That is why you increment intensity: you are recruiting more axons, not inflating each axon's spike height.

If intensity is already high and the SNAP is still absent, the physiology changes: technical error (wrong nerve, reversed anode/cathode in a way that fails to depolarize under the intended site, recording electrodes off the nerve), conduction failure between stimulus and recording sites, or axonal loss. Subthreshold silence on the first low-intensity trial is the expected first step, not pathology.

Putting phases on the laboratory timeline

A myelinated sensory AP at a node lasts on the order of 0.5–1 ms. The SNAP you see is longer because it is a dispersion of many axons with slightly different velocities and start times, plus volume-conductor filtering. CMAP duration is longer still because neuromuscular delay and muscle-fiber APs add temporal spread. Do not confuse the 1 ms intracellular spike with the 5–15 ms CMAP envelope.

OpenExamPrep takeaway chain: threshold → Na+ upstroke → Na+ inactivation plus K+ efflux → undershoot → refractory recovery. Single axon all-or-none; SNAP/CMAP amplitude graded by recruitment. Subthreshold means no regenerative Na+ current and therefore no SNAP. Very fast repetition can fail because the membrane has not left the refractory window.