Action Potentials: Mechanisms, Properties, and Conduction in Neurons

Action Potentials in Neurons

Introduction to Action Potentials

Action potentials are rapid, transient changes in membrane potential that serve as the fundamental electrical signals in neurons. They enable the long-distance transmission of information along axons, ultimately leading to neurotransmitter release at synapses.

• Definition: An action potential (AP) is a stereotyped, all-or-none depolarization of the neuronal membrane, typically from a resting potential (~ -65 mV) up to about +40 mV.

• Initiation: APs are initiated at the axon hillock and propagate along the axon.

• Function: The primary function of an AP is the rapid, long-distance transmission of information within the nervous system.

Properties of Action Potentials

Key Characteristics

• Constant Amplitude and Duration: APs have a consistent amplitude (~100 mV) and duration (2–3 ms) in a given neuron type.

• Always Depolarizing: APs are always depolarizing events (membrane potential becomes less negative).

• All-or-None Principle: APs occur only if the membrane depolarization reaches a threshold (typically ~10 mV above rest). Subthreshold stimuli do not elicit APs.

• Threshold: The minimum depolarization required to trigger an AP.

• Refractory Periods: APs have two refractory periods:

  • Absolute Refractory Period: A phase during which no new AP can be generated, regardless of stimulus strength. Occurs during the falling phase of the AP.

  • Relative Refractory Period: A phase during which a stronger-than-normal stimulus is required to generate another AP. Occurs during the undershoot phase.

• Propagation Without Decrement: APs travel along the axon without decreasing in amplitude.

Table: Comparison of Absolute and Relative Refractory Periods

Refractory Period	Ability to Generate AP	Timing
Absolute	Impossible	During falling phase
Relative	Possible with strong stimulus	During undershoot

Action Potential Waveform and Phases

Phases of the Action Potential

• Resting State: Membrane at resting potential (~ -65 mV).

• Depolarization: Rapid influx of Na+ ions through voltage-gated Na+ channels causes the membrane potential to become positive.

• Repolarization: Na+ channels inactivate, and voltage-gated K+ channels open, allowing K+ efflux and return toward resting potential.

• Hyperpolarization (Undershoot): Membrane potential temporarily becomes more negative than resting due to continued K+ efflux.

• Return to Rest: K+ channels close, and the membrane returns to resting potential.

Mechanisms of Action Potential Generation

Voltage-Gated Ion Channels

• Voltage-Gated Na+ Channels: Open rapidly in response to depolarization (~10 mV above rest), allowing Na+ influx. Inactivate after ~1 ms.

• Voltage-Gated K+ Channels: Open more slowly (after ~1 ms delay), allowing K+ efflux, which repolarizes the membrane.

Table: Ion Concentrations and Equilibrium Potentials

	Na+	K+
Extracellular [EC]	150 mM	5 mM
Intracellular [IC]	15 mM	100 mM
Equilibrium Potential (Eion)	+62 mV	-80 mV

Forces Influencing Ion Movement

• Diffusion Force: Ions move from high to low concentration.

• Electrostatic Force: Ions move according to electrical gradients.

• Driving Force: The net force (combination of diffusion and electrostatic) that determines ion movement.

Equations

• Nernst Equation: Determines the equilibrium potential for a given ion: $E_{ion} = \frac{RT}{zF} \ln \left( \frac{[ion]_{out}}{[ion]_{in}} \right)$

Patch-Clamp Technique

Experimental Evidence

• Patch-Clamping: A technique developed by Sakmann and Neher (Nobel Prize 1991) to measure currents through individual ion channels.

• Findings:

  • Na+ channels open rapidly (latency in microseconds) and inactivate even if depolarization continues.

  • K+ channels open with a delay (~1 ms) and do not inactivate during depolarization.

Conduction Velocity of Action Potentials

Determinants of Conduction Velocity

• Axon Diameter: Larger diameter axons have lower internal resistance, increasing conduction velocity.

• Membrane Resistance (Rm): Increased by myelination, which reduces ion leakage and increases speed.

• Maximum Velocity: Up to 100 meters/second in myelinated vertebrate axons; much slower in most neurons.

Table: Strategies to Increase Conduction Velocity

Strategy	Mechanism	Example
Increase Axon Diameter	Lower internal resistance	Invertebrates (giant axons)
Increase Membrane Resistance (Rm)	Myelination	Vertebrates

Myelination and Its Effects

Role of Myelin

• Myelin Sheath: Formed by oligodendrocytes (CNS) or Schwann cells (PNS), wraps around axons to increase membrane resistance.

• Effect: Reduces leakage of positive ions, allowing the action potential to travel faster and farther.

Summary Table: Key Properties of Action Potentials

Property	Description
Amplitude	~100 mV
Duration	2–3 ms
Threshold	~10 mV above rest
Propagation	All-or-none, without decrement
Refractory Periods	Absolute (~1 ms), Relative (~3 ms)
Conduction Velocity	Up to 100 m/s (myelinated)

Additional info:

• Action potentials are essential for neural coding, but their stereotyped nature means that information is encoded in the frequency of APs, not their shape or size.

• Myelination is a key evolutionary adaptation for rapid signal transmission in vertebrates.