Neurophysiology: Membrane Potentials and Action Potential Propagation

Membrane Potentials and Rest State Dynamics

• Definition of Resting Membrane Potential:

  • The resting membrane potential represents the baseline electrical charge difference across a cell membrane when the cell is at rest and performing no active work.
  • In a resting neuron, the inner surface of the plasma membrane carries a net negative charge relative to the outer surface, valued at approximately $-70\,\text{mV}$.

• Electrical Basis of Resting Potential:

  • Ion Concentration Gradients:
  • Sodium ($\text{Na}^+$) concentration is highest on the outside of the cell in the extracellular fluid.
  • Potassium ($\text{K}^+$) concentration is highest on the inside of the cell in the intracellular fluid.
  • Differential Membrane Permeability:
  • At rest, the cell membrane is significantly more permeable to potassium ($\text{K}^+$) than to sodium ($\text{Na}^+$).
  • Potassium continuously diffuses out of the cell down its concentration gradient through open potassium leakage channels, leaving behind uncompensated negative intracellular charges.

Graded Potentials

• Definition and Core Characteristics:

  • A graded potential is a short-lived, highly localized change in the membrane potential.
  • Involves minor fluctuations causing small degrees of depolarization or repolarization/hyperpolarization.
  • Designed strictly for short-distance or short-term local communication; signals do not propagate across long distances.

• Magnitude and Distance Relationships:

  • The response magnitude and distance traveled depend directly on the strength of the triggering stimulus.
  • Local current flows away from the stimulus site, but electrical charge leakage causes the signal to fade out and decay completely as distance increases.

• Analogy of Ripples in a Water Pool:

  • Imagine a completely calm, still body of water with no wind or wave action.
  • Dropping a small pebble creates minor ripples that dissipate rapidly and travel only a very short distance.
  • Dropping a massive boulder creates large splash waves that travel significantly further across the water before fading away.
  • In a graded potential, a minor stimulus acts like a pebble (producing tiny, localized potential changes), whereas a larger stimulus acts like a boulder (causing a broader spread before decaying).

• Context-Specific Terminology:

  • Receptor Potential: A graded potential produced at sensory receptor terminals, such as those located in the eye or ear.
  • Postsynaptic Potential: A graded potential generated at the postsynaptic membrane of a neuron at a synapse.

Action Potentials and Nerve Impulses

• Definition and Function:

  • Action potentials (commonly called nerve impulses) are rapid, high-magnitude electrical signals used by neurons and muscle tissue for long-distance communication.
  • Critical for all physical sensations and responses, including sight, hearing, taste, and motor execution.
  • Unlike graded potentials, action potentials do not decrease in magnitude (amplitude) as they move along the cell; they regenerate continuously without decaying.

• Anatomic Origin and Trajectory:

  • Most action potentials originate in the initial segment of the axon, also known as the trigger zone.
  • The membrane potential swings from a resting state of $-70\,\text{mV}$ up to a positive peak value of $+30\,\text{mV}$, then repolarizes rapidly back down to $-70\,\text{mV}$ following a temporary hyperpolarization phase.

Key Ion Channels Involved in Action Potentials

• Voltage-Gated Channels:

  • Specialized ion channels that open or close in response to direct changes in the surrounding membrane potential.
  • Voltage-Gated Sodium Channels: Contain gates that open rapidly when voltage hits threshold, driving massive inward sodium movement.
  • Voltage-Gated Potassium Channels: Open more slowly at peak depolarization, allowing outward potassium movement.

• Leakage Channels:

  • Non-gated channels that remain open continuously; resting potassium leakage channels allow passive outflow of $\text{K}^+$ down its concentration gradient.

Step-by-Step Phases of Action Potential Generation

• 1. Resting State:

  • All voltage-gated sodium ($\text{Na}^+$) and potassium ($\text{K}^+$) channels are closed.
  • The resting membrane potential is maintained at $-70\,\text{mV}$.

• 2. Threshold and Depolarization:

  • A localized depolarizing stimulus shifts the membrane potential from $-70\,\text{mV}$ up to the critical threshold level of $-55\,\text{mV}$ (or between $-50\,\text{mV}$ and $-55\,\text{mV}$).
  • Reaching threshold triggers the immediate opening of voltage-gated sodium channels.
  • Sodium Influx: Sodium ($\text{Na}^+$) rushes into the intracellular space down both its concentration gradient (high outside to low inside) and electrical gradient.
  • Positive Feedback Loop: As positive sodium ions enter, the internal potential becomes more positive, which opens additional voltage-gated sodium channels. This explosive positive feedback drives the membrane potential rapidly up to $+30\,\text{mV}$.

• 3. Repolarization:

  • At peak potential ($+30\,\text{mV}$), voltage-gated sodium channel inactivation gates close, shutting off further sodium entry.
  • Simultaneously, voltage-gated potassium channels open fully.
  • Potassium Efflux: Potassium ($\text{K}^+$) rushes out of the cell down its concentration gradient (high inside to low outside).
  • The outward transfer of positive electrical charges repolarizes the cell, driving the internal membrane potential back down toward negative levels.

• 4. Hyperpolarization:

  • Voltage-gated potassium channels close slowly, permitting excess potassium ions to exit.
  • This causes the membrane potential to temporarily dip below $-70\,\text{mV}$ before returning to baseline.

• 5. Restoring Ion Distributions via the Sodium-Potassium Pump:

  • While repolarization restores electrical potential, ionic concentrations are temporarily reversed ($\text{Na}^+$ inside, $\text{K}^+$ outside).
  • The active Sodium-Potassium Pump ($\text{Na}^+/\text{K}^+$ ATPase) moves $\text{Na}^+$ back out of the cell and $\text{K}^+$ back into the cell against their respective concentration gradients.
  • This transport process requires cellular energy in the form of ATP.

Propagation of Action Potentials

• Continuous Propagation:

  • Occurs in unmyelinated axons.
  • The electrical current spreads sequentially across every adjacent patch of axonal membrane, bringing downstream segments to threshold step-by-step.
  • Conduction velocity is continuous and slow, rarely exceeding $2\,\text{m/s}$.

• Saltatory Propagation:

  • Occurs in myelinated axons.
  • Myelin Sheath Structure: Fatty, multi-layered glial insulation wrapping around the axon, interrupted at regular intervals by exposed membrane nodes known as Nodes of Ranvier.
  • Mechanism: Voltage-gated sodium channels are highly concentrated at the Nodes of Ranvier and largely absent underneath myelin. The electrical current leaps (hops) rapidly from node to node.
  • Conduction velocity is extremely fast, frequently exceeding $100\,\text{m/s}$.

• Sprinting Analogy for Saltatory Conduction:

  • Continuous propagation is like walking step-by-step touching every point on the ground.
  • Saltatory conduction is like high-speed Olympic sprinters who spend minimal time touching the track, leaping or floating through the air from point to point.

• Pathological Context - Multiple Sclerosis (MS):

  • MS is an autoimmune/viral condition that targets and destroys the myelin sheath.
  • Loss of myelin destroys saltatory conduction, reducing action potential speed from $100\,\text{m/s}$ down toward $2\,\text{m/s}$, severe impairing nerve signal transmission.

Frequency Encoding of Stimulus Intensity

• Constancy of Amplitude:

  • The amplitude (size/peak potential) of an action potential is independent of stimulus strength.
  • Once threshold is reached, an action potential always fires at full amplitude ($+30\,\text{mV}$).

• Frequency Coding Mechanism:

  • Sub-threshold stimuli generate zero action potentials.
  • Weak suprathreshold stimuli produce a low frequency of action potentials (few impulses per second).
  • Stronger suprathreshold stimuli produce a high frequency of action potentials (rapid succession of impulses).
  • The nervous system distinguishes a strong stimulus from a weak stimulus based on the frequency of action potentials transmitted to the brain, not their size.

Refractory Periods

• Definition and Importance:

  • A period during and after an action potential when the membrane is resistant to generating subsequent impulses.
  • Enforces unidirectional signal flow down the axon and prevents over-excitation.

• Absolute Refractory Period:

  • Timeframe from sodium channel activation until sodium channels begin resetting.
  • Voltage-gated sodium channels are completely inactivated/closed and unresponsive.
  • No stimulus, regardless of its strength, can initiate another action potential during this time.
  • Capacity Gate Analogy: A venue gatekeeper restricted to letting only five people in. Once maximum capacity is hit, no amount of money offered ($1000\,\text{dollars}$ or $2000\,\text{dollars}$) can force the gate open until full recovery occurs.
  • Mechanical Reload Analogy: A firearm that cannot fire a second round until the physical mechanical action reloads a new shell.

• Relative Refractory Period:

  • Follows the absolute refractory period during repolarization and hyperpolarization.
  • Most sodium channels have returned to their resting state, but potassium channels remain open.
  • A secondary action potential can be triggered, but only if the stimulus is significantly stronger than normal.

Factors Influencing Conduction Velocity

• Myelination:

  • Axons wrapped in myelin conduct impulses at speeds up to $100\,\text{m/s}$ via saltatory conduction, compared to unmyelinated axons conducting at $2\,\text{m/s}$.

• Axon Diameter:

  • Larger diameter axons present lower internal resistance to ion flow, enabling faster conduction velocities than smaller diameter axons.