Action potential according Sembulingm for knrush university exam
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Action Potential (Sembulingam-style) - KNRush University Exam
Based on standard physiology textbooks (Guyton & Hall, Costanzo) that form the backbone of Sembulingam's content.
1. Definition
An action potential is a rapid, transient change in the membrane potential of an excitable cell (nerve/muscle) from its resting negative value to a positive value and back again. It is the electrical signal used to transmit information along nerve fibers and trigger muscle contraction.
2. Resting Membrane Potential (RMP)
Before an action potential can occur, the membrane must be at rest.
| Parameter | Value |
|---|---|
| RMP of large nerve fibers | -70 mV (inside negative) |
| Na⁺ outside | 142 mEq/L |
| Na⁺ inside | 14 mEq/L |
| K⁺ outside | 4 mEq/L |
| K⁺ inside | 140 mEq/L |
Basis of RMP:
- The Na⁺-K⁺ ATPase pump (electrogenic) transports 3 Na⁺ out and 2 K⁺ in per cycle - creating a net negative interior charge.
- K⁺ "leak" channels allow K⁺ to diffuse outward down its concentration gradient, further negativizing the interior.
- Large intracellular impermeant anions (proteins, phosphates, sulfates) cannot leave the cell and contribute to interior negativity.
At rest, the membrane is about 100x more permeable to K⁺ than to Na⁺.
3. Phases of the Action Potential
Phase 1 - Resting Stage
- Membrane potential = -70 mV
- Membrane is "polarized"
- Voltage-gated Na⁺ channels: CLOSED (activation gate shut, inactivation gate open)
- Voltage-gated K⁺ channels: CLOSED
Phase 2 - Depolarization
- A stimulus raises the membrane potential toward the threshold (-55 mV, i.e., ~15 mV rise from resting)
- At threshold, a positive-feedback cycle (Hodgkin cycle) is triggered:
- Na⁺ channels open → Na⁺ rushes IN → membrane potential rises → more Na⁺ channels open → explosive depolarization
- Na⁺ permeability increases 500-5000 fold
- Membrane potential swings from -70 mV to +35 mV (overshoot beyond zero)
- The portion where membrane potential goes positive is called the overshoot (or spike peak)
Phase 3 - Repolarization
- Within a fraction of a millisecond after Na⁺ channels open, the inactivation gate of Na⁺ channels closes (slower process)
- Simultaneously, voltage-gated K⁺ channels open (delayed response)
- K⁺ diffuses rapidly outward → restores negative membrane potential
- Na⁺ conductance falls; K⁺ conductance rises ~30-fold
Phase 4 - Hyperpolarization (After-Depolarization / Undershoot)
- K⁺ channels remain open slightly longer than needed
- Membrane potential briefly goes more negative than RMP (below -70 mV)
- Called the after-hyperpolarization or undershoot
- K⁺ channels then close and membrane returns to -70 mV
4. Ionic Conductance Changes During Action Potential
| Phase | Na⁺ Conductance | K⁺ Conductance |
|---|---|---|
| Resting | Low (baseline) | Moderate (leak) |
| Depolarization | Rises 5000x (fast) | Slightly delayed rise |
| Repolarization | Falls (inactivation) | Peaks ~30x |
| Hyperpolarization | Near zero | Still slightly elevated |
5. Voltage-Gated Channels - Sembulingam Key Points
Voltage-Gated Na⁺ Channel (has 2 gates)
| Gate | Resting State | Activated State | Inactivated State |
|---|---|---|---|
| Activation gate (outer) | CLOSED | OPEN | CLOSED |
| Inactivation gate (inner) | OPEN | OPEN → closing | CLOSED |
- Activation threshold: ~-55 mV (15 mV above RMP)
- Once inactivated, the Na⁺ channel CANNOT reopen until the membrane repolarizes back toward RMP - this is the basis of the absolute refractory period.
Voltage-Gated K⁺ Channel (1 gate - delayed rectifier)
- Opens slowly compared to Na⁺ channels
- Opens during late depolarization/repolarization phase
- Responsible for rapid repolarization and after-hyperpolarization
6. Threshold and "All-or-None" Law
- Threshold potential = -55 mV (approximately)
- A stimulus must raise the membrane potential by 15-30 mV above RMP to reach threshold
- Below threshold: subthreshold stimulus → local, graded potential only → no action potential
- At or above threshold: full-sized action potential fires - this is the All-or-None Law
- The size and shape of the action potential do not change with stimulus intensity
- More intense stimulation increases the frequency (rate) of firing, not the amplitude
7. Propagation of the Action Potential
- An action potential at one point creates local current circuits with adjacent resting membrane
- Depolarized region (positive inside) attracts current flow to the negative resting areas → raises adjacent membrane to threshold → fires new action potential
- Propagation is unidirectional in practice (because the region behind is in the refractory period)
- In unmyelinated fibers: propagation is continuous along the entire axon membrane (slower)
- In myelinated fibers: propagation is saltatory conduction - jumps from one node of Ranvier to the next (much faster, more energy efficient)
Velocity of conduction:
- Large myelinated fibers (A fibers): up to 120 m/s
- Small unmyelinated C fibers: 0.5-2 m/s
8. Refractory Periods
Absolute Refractory Period (ARP)
- During depolarization + early repolarization
- Na⁺ channels are in the inactivated state (inactivation gate closed)
- No stimulus, however strong, can produce another action potential
- Corresponds to the spike of the action potential (~1 ms in nerve)
- Ensures unidirectional propagation and limits maximum firing rate
Relative Refractory Period (RRP)
- Follows the ARP, during late repolarization and after-hyperpolarization
- Na⁺ channels begin to recover (reset to resting state)
- K⁺ channels still partially open (membrane more negative than normal)
- A stronger-than-normal stimulus can trigger an action potential
- Action potential produced is smaller in amplitude
9. After-Potentials
| After-Potential | Timing | Mechanism |
|---|---|---|
| After-depolarization (negative after-potential) | Immediately after spike | Accumulation of K⁺ outside membrane |
| After-hyperpolarization (positive after-potential) | Follows after-depolarization | Prolonged K⁺ channel opening; membrane more negative than RMP |
10. Characteristics of Action Potential (Exam Summary)
| Property | Detail |
|---|---|
| All-or-None | Yes - fires fully or not at all |
| Amplitude | ~105 mV (from -70 to +35 mV) |
| Duration | ~1 ms (nerve); longer in cardiac/smooth muscle |
| Threshold | ~-55 mV |
| Propagation | Bidirectional along axon but effectively unidirectional due to refractoriness |
| Overshoot | Membrane potential goes positive (due to Na⁺ influx) |
| Non-decremental | Does not diminish with distance (unlike graded potentials) |
11. Factors Affecting Action Potential
| Factor | Effect |
|---|---|
| Hypocalcemia (↓ Ca²⁺) | ↑ excitability (lowers threshold); can cause spontaneous firing/tetany |
| Hypercalcemia | ↓ excitability (raises threshold) |
| Local anaesthetics (e.g., lidocaine) | Block voltage-gated Na⁺ channels → prevent depolarization |
| Tetrodotoxin (TTX) | Specifically blocks Na⁺ channels |
| Tetraethylammonium (TEA) | Blocks K⁺ channels |
| Myelination | Increases conduction velocity (saltatory conduction) |
Quick Revision Table for Exam
| Stage | Membrane Potential | Key Ion Movement | Gate Status |
|---|---|---|---|
| Resting | -70 mV | K⁺ leak out slowly | Na⁺ act. gate CLOSED |
| Depolarization | -70 → +35 mV | Na⁺ rushes IN | Na⁺ act. gate OPEN |
| Repolarization | +35 → -70 mV | K⁺ rushes OUT | Na⁺ inact. gate CLOSED; K⁺ gate OPEN |
| After-hyperpolarization | Below -70 mV | K⁺ still leaving | K⁺ gate slowly closing |
| Recovery | Returns to -70 mV | Na⁺-K⁺ pump restores | All channels resting |
Sources: Guyton and Hall Textbook of Medical Physiology (14e) - Ch. 5; consistent with Sembulingam's Essentials of Medical Physiology framework.
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