Stimuli and local response
For a cell to become excited, a stimulus must act upon it. Stimuli are divided into subthreshold, threshold, and suprathreshold.
With a weak (subthreshold) stimulus, the resting potential decreases only slightly at the electrode application site. A local response (LR) occurs. Its main feature is a direct relationship: the stronger the stimulus, the higher the response amplitude.
If the stimulation reaches the threshold value, the local response reaches the critical depolarization level (CDL). It is at this exact moment that the local change turns into a full-fledged action potential.
Dynamics and phases of the action potential
The development of excitation includes several successive stages that are displayed on a graph:
- Pre-spike: slow partial depolarization corresponding to the local response.
- Depolarization (Spike, peak): a sharp voltage jump. The charge shifts from the critical level (-50 mV) to positive values (e.g., +30 mV). This phenomenon of charge reversal is called inversion or overshoot (the inner surface of the membrane becomes positive).
- Repolarization: voltage drop and return to the resting level. At the end of this phase, a negative after-potential (NAP) — after-depolarization — may be observed.
- After-hyperpolarization: the charge drops below the initial -70 mV. This is referred to as a positive after-potential (PAP).
The duration and shape of these phases depend on the tissue. In neurons and skeletal myocytes, the spike is very short, and the presence of after-potentials is variable.
Ionic mechanisms and channel function
All potential changes are driven by tube-shaped membrane proteins known as ion channels.
- Resting state: The membrane potential is -70 mV. Potassium channels are closed. Sodium channels are also closed but ready for action: their activation m-gates are shut, and inactivation h-gates are open. There is more potassium inside the cell and more sodium outside.
- Onset of stimulation (LR): m-gates begin to open slowly, but the inward sodium current is negligible.
- Depolarization phase: Upon reaching the threshold (-50 mV), all m-gates open. An avalanche-like, passive influx of Na⁺ ions begins down their concentration gradient.
- Repolarization: The incoming positive charge causes the h-gates to close (inactivation of sodium channels). Simultaneously, the "charge sensors" of the potassium pores react, causing them to open. K⁺ ions rush outward, restoring the negative charge inside.
- Hyperpolarization and recovery: Since potassium channels close slowly, potassium efflux continues (sometimes joined by Cl⁻ influx), driving the charge below -70 mV. The original balance is ultimately restored by the Na⁺,K⁺-ATPase, which actively pumps ions back. Sodium channels reset (closing m-gates and opening h-gates), and the cell is ready for a new impulse.
All-or-none law
This law reflects the constancy of the action potential amplitude. Its essence is simple:
- To a subthreshold stimulus, the cell gives no impulse ("none").
- To a threshold and suprathreshold stimulus, an AP of the maximum possible amplitude for this cell occurs ("all").
Single structures obey this law: neurons, individual nerve and muscle fibers, smooth muscles, and cardiac tissue. However, whole nerve trunks or skeletal muscles do not obey it. This is because they consist of multiple fibers with varying excitability thresholds.
Briefly: answers to topical questions
How does a local response differ from an action potential?
A local response occurs in response to a subthreshold stimulus, whereas an action potential occurs in response to a threshold or suprathreshold stimulus. Unlike an AP, a local response cannot propagate over significant distances (propagates with decrement and fades quickly), does not obey the all-or-none law (its amplitude depends gradiently on the stimulus strength), is capable of summation, and lacks a refractory period.
| Sign | Local response | Action potential |
|---|---|---|
| Stimulus | Subthreshold | Threshold/suprathreshold |
| Propagation | Does not propagate / with decrement | Propagates without decrement |
| Summation | Possible | Impossible |
| Law | Strength (graded) | All-or-none |
| Refractoriness | Absent | Present |
What is the conduction velocity of an action potential in myelinated and unmyelinated nerve fibers?
Conduction velocity depends on the presence of a myelin sheath and fiber diameter: myelinated fibers conduct faster than unmyelinated ones, and thick fibers faster than thin ones. In myelinated fibers, conduction is saltatory, so the propagation velocity of excitation is higher than in continuous conduction.
- Myelinated fibers: these include type A and B fibers. The fastest are type Aα fibers, with a velocity of about 100 m/s; A-δ fibers conduct at 4–30 m/s; for myelinated fibers of the depressor nerve, a velocity of up to 10 m/s is reported.
- Unmyelinated fibers: these include type C fibers. They are the slowest: velocity is about 1 m/s; a velocity of 0.5–2 m/s is also reported for C fibers.
What is absolute refractoriness and which phase of the AP does it correspond to?
Absolute refractoriness is a period of complete membrane inexcitability when the generation of a new action potential is impossible; the stimulation threshold during this period approaches infinity, and excitability is zero. It is associated with the temporary inactivation of sodium channels; absolute refractoriness is caused by the inactivation of the majority of Na⁺ channels.
Absolute refractoriness occurs during the spike period: the depolarization phase and, according to literature on muscle contraction, the initial repolarization phase of the AP.
How to remember the gates of the sodium channel at rest: M (m-gates) — Make entry impossible (closed), while H (h-gates) — Hang open (open).
Class and exam questions
What is the role of the sodium-potassium pump during spike generation?
The pump itself does not participate in the fast phases of depolarization and repolarization. Its task is to restore the initial ion concentrations after the action potential has already completed.
Why doesn't the AP amplitude increase with stronger stimulation?
In accordance with the "all-or-none" law, even at threshold stimulation, all available sodium channels open, providing a maximum ion current. The cell simply cannot respond more strongly.
What else to study on this topic
- Features of AP generation in cardiomyocytes and smooth muscle
- The role of chloride ions in the formation of after-hyperpolarization
- The mechanism of voltage-gated charge sensors in potassium channels
- Constitutively open leakage potassium channels and maintenance of the resting membrane potential
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