Action Potential Phases and Mechanisms

Action Potential and Nerve Impulse

An action potential is a fundamental electrical signal used by excitable cells, primarily neurons and muscle cells, to transmit information rapidly over long distances. It involves a fast, abrupt, and temporary change in the membrane potential, characterized by depolarization, reversal, and subsequent restoration of the resting membrane potential.

General Characteristics of Excitable Cells

• Excitable cells (nerve and muscle cells) are capable of generating action potentials.

• Their excitability stems from specific regulated ion channels in their membranes that alter permeability.

• Action potentials are crucial for transferring information throughout the body.

Membrane Potential Changes and Electrical Signals

Changes in membrane permeability, often due to the opening of ion channels, lead to changes in membrane potential from the typical resting potential of a neuron, which is approximately -70mV.

Two Types of Electrical Signals

Graded Potentials

A graded potential is a small deviation from the resting membrane potential, making the membrane either more or less polarized.

• They vary in amplitude based on stimulus strength.

• They are localized and conduct decrementally.

• Occur primarily in the dendrites and cell body of a neuron, and in dendrites of sensory neurons.

• Small deviations from -70mV:

  • Hyperpolarization: The inside of the membrane becomes more negative.

  • Depolarization: The inside of the membrane becomes more positive.

• Duration: a few milliseconds to seconds.

• Undergo summation (addition of potentials in time and space).

• Involve mechanically-gated or ligand-gated ion channels (usually Na+, K+, or Cl−).

Ionic Basis of Graded Potentials

Ion movement across the membrane influences the type of graded potential:

• Depolarizing Graded Potential (more positive inside):

  • Na+ entry (opens Na+ channels).

  • Ca2+ entry (opens Ca2+ channels).

  • Closure of K+ channels.

• Hyperpolarizing Graded Potential (more negative inside):

  • Cl− entry (opens Cl− channels).

  • K+ exit (opens K+ channels).

  • Closure of Na+ or Ca2+ channels.

These potentials are initiated by stimuli such as mechanical pressure (mechanically-gated channels) or neurotransmitters (ligand-gated channels).

Action Potential: Nerve Impulse

An action potential is a rapid, transient, and self-propagating change in the membrane potential of an excitable cell. It is an "all-or-none" event, meaning if the stimulus reaches a certain threshold, the action potential will occur with maximal amplitude; otherwise, it won't occur at all.

General Characteristics

• Occurs only when the threshold potential (approximately -55mV) is reached.

• "All-or-none" response; constant amplitude (approx. 100mV, peaking at +30mV).

• Does not decrease in amplitude as it propagates.

• Driven by voltage-gated ion channels.

• Duration of a nervous action potential is approximately 1-2 milliseconds.

• Unidirectional propagation.

• Information is encoded by the frequency of impulses and the number of neurons activated, not by amplitude.

Phases of the Action Potential

The action potential involves distinct phases:

1. Resting Phase:

   • The membrane is at its resting potential (-70mV).

   • Voltage-gated Na+ channels are in the resting (closed) state.

   • Voltage-gated K+ channels are closed.

2. Depolarizing Phase (Rising Phase):

   • A stimulus causes the membrane potential to depolarize towards the threshold potential (-55mV) at the axon hillock (trigger zone with high density of voltage-gated Na+ channels).

   • Once threshold is reached, voltage-gated Na+ channels open rapidly.

   • Na+ rushes into the cell due to its electrochemical gradient, causing rapid depolarization.

   • A positive feedback loop occurs, opening more Na+ channels and driving the membrane potential to a peak of about +30mV.

3. Repolarizing Phase (Falling Phase):

   • The depolarization phase terminates as voltage-gated Na+ channels inactivate (a time-dependent process).

   • Simultaneously, voltage-gated K+ channels, which open more slowly, reach their maximum opening around the peak of the action potential.

   • K+ flows out of the cell, making the interior more negative and restoring the resting membrane potential.

4. Hyperpolarizing Phase (Undershoot/After-hyperpolarization):

   • Kv channels remain open for a brief period even after the resting potential is reached, causing excess K+ efflux.

   • This results in a temporary hyperpolarization, making the membrane potential more negative than the resting potential.

   • Eventually, the Kv channels close.

5. Re-establishing Resting State:

   • The Na+/K+-ATPase pump actively restores the initial Na+ and K+ concentration gradients across the membrane, although ion concentration changes during a single action potential are minimal.

Voltage-Gated Sodium Channels

These channels have two gates:

1. Activation gate:

   • At resting potential, the activation gate is closed.

   • At threshold potential, the activation gate opens, allowing Na+ influx.

2. Inactivation gate:

   • Opens at resting potential.

   • During the peak of the action potential, the inactivation gate closes, terminating Na+ flow and initiating repolarization.

Refractory Period

The refractory period is a crucial time during and after an action potential when the neuron's excitability is altered, preventing overlapping action potentials and ensuring unidirectional propagation.

• Absolute Refractory Period:

  • Occurs during depolarization and the early part of repolarization.

  • A neuron cannot generate another action potential, regardless of stimulus strength.

  • This is because voltage-gated Na+ channels are either open or in an inactivated state and must return to the resting (closed) state before they can reopen.

  • Ensures individual, distinct action potentials and sets an upper limit on firing frequency.

• Relative Refractory Period:

  • Occurs during the later phase of repolarization and hyperpolarization.

  • A supra-threshold stimulus (stronger than normal) can trigger another action potential.

  • During this period, some voltage-gated Na+ channels have reset to their resting state, but K+ channels are still open, making the membrane more negative and resistance to further depolarization higher.

Propagation of the Action Potential (Nerve Impulse)

An action potential propagates along the axon membrane by affecting adjacent areas. As Na+ enters during depolarization, local currents develop, depolarizing neighboring membrane regions and opening their voltage-gated Na+ channels. This self-propagating wave of depolarization is called a nerve impulse.

The action potential itself does not "travel" but rather is regenerated at each point along the axon.

Conduction Speed

The speed at which an action potential propagates is influenced by two main factors:

1. Diameter of the Nerve Fiber (Axon):

   • Wider axons offer less resistance to the flow of internal current, leading to faster conduction.

2. Myelination:

   • The myelin sheath is an insulating layer around axons that significantly increases conduction speed.

   • It reduces current loss across the membrane.

   • Myelin acts like an electrical insulator, effectively increasing the thickness of the membrane and reducing flow resistance.

   • Action potentials only occur at the Nodes of Ranvier, gaps in the myelin sheath where voltage-gated ion channels are concentrated.

   • This type of propagation is called saltatory conduction (from Latin saltare, to jump), where the impulse "jumps" from one node to the next.

Saltatory Conduction vs. Continuous Conduction

Summary of Action Potential Characteristics

• Generated when depolarization at the axon hillock reaches the threshold potential.

• Involves opening of voltage-dependent Na+ channels (causing depolarization) followed by opening of K+ channels and inactivation of Na+ channels (causing repolarization).

• Followed by absolute and relative refractory periods, preventing immediate re-firing and ensuring unidirectional flow.

• Conduction speed is determined by axon diameter and myelination.