brain

Action Potentials and Neural Conduction

Historical Background: The Action Potential

• Psychic Pneuma (Herophilus & Galen, ~200 BCE):
  • Nerves carried an invisible “air-like” substance responsible for perception and action.
  • Thought to flow from brain ventricles into nerves.
• Luigi Galvani (1737–1798):
  • Demonstrated that nerves conduct electrical signals.
  • Famous frog-leg experiments with static electricity.
• Johannes Müller (1801–1858):
  • Law of Specific Nerve Energies: different nerves carry specific types of information (optic nerve → vision, auditory nerve → sound).
  • Experience is determined by the pathway, not the stimulus.
• Hermann von Helmholtz (1821–1894):
  • Measured speed of nerve conduction.
  • Developed the ophthalmoscope, color vision theory, and audition theory.

The Action Potential

Basics

• Begins at the axon hillock.
• Travels down axon without decreasing in size (non-decremental).
• Is an all-or-none electrical event.

Hodgkin & Huxley (1940s)

• Used the squid giant axon to measure membrane potentials.
• Found:
  • At rest: inside = negative (~–70 mV).
  • Depolarization beyond a threshold (~–65 mV) triggers an action potential.

Phases of the Action Potential

1. Resting Potential – K⁺ channels partly open; Na⁺ channels closed.
2. Depolarization – Na⁺ channels open rapidly, Na⁺ floods in. (See Drugs and Pharmacology for how drugs block these channels)
3. Rising Phase (Upstroke) – rapid influx of Na⁺.
4. Falling Phase (Downstroke) – Na⁺ channels close; K⁺ channels fully open, K⁺ exits.
5. Afterhyperpolarization – K⁺ continues leaving, cell becomes more negative than resting.
6. Return to Resting – sodium-potassium pump restores gradients (3 Na⁺ out, 2 K⁺ in).

Ion Forces

• Diffusion: ions move down concentration gradients.
• Electrostatic force: opposite charges attract, like charges repel.

Refractory Periods

• Absolute refractory period: no new action potential possible (Na⁺ channels inactive).
• Relative refractory period: requires stronger stimulation (membrane hyperpolarized).

All-or-None Law

• Action potential magnitude is the same, regardless of stimulus strength.
• Stronger stimulus only increases firing frequency, not spike size.

Propagation of the Action Potential

• Moves actively along axon by sequential depolarization of adjacent regions.
• Saltatory conduction: in myelinated axons, AP “jumps” between nodes of Ranvier → faster and more efficient.
• Passive Conduction: in unmyelinated axons, slower

Multiple Sclerosis (MS)

• An autoimmune disorder where the body attacks myelin.
• Results in slower or blocked conduction of nerve impulses.
• Symptoms:
  • Muscle weakness
  • Sensory problems
  • Cognitive deficits
• Course:
  • Stage 1: intermittent symptoms.
  • Stage 2: progressively worsening.

Genetic Risk

• Higher prevalence among people of European ancestry.
• Numerous genetic variants linked to MS susceptibility.
• Recent research: risk increased in steppe pastoralist populations (historical genetic emergence).

Multiple Sclerosis Mechanism

• MS is an autoimmune disease: the immune system attacks myelin.
• Genetic factors: More common in people of European ancestry; many genetic variants involved.
• Mechanism:
  • Leaky blood-brain barrier allows lymphocytes into the brain.
  • These, along with microglia, release inflammatory substances.
  • Myelin segments break down → disrupts saltatory conduction.
  • Downstream of the demyelinated region, the axon withers away and an axonal ovoid is formed
• Gut-brain connection: Dysbiosis (imbalanced microbiome) weakens intestinal wall, allowing microbial products to enter bloodstream → increases inflammation and BBB leakage.