Neurophysiology: From Resting Potential to Multiple Sclerosis

Neuron Structure & Directionality

• Multipolar neuron is the "standard picture" used.
  • Components: many short, branched dendrites → large cell body (soma / neurosoma) → single long axon → synaptic terminals.
  • Signal ALWAYS travels from soma toward synaptic terminal (anterograde flow); only rare exceptions.
• Post-synaptic elements (drawn in purple) sit across the synaptic cleft and will be the next cell to respond.
• Narrowing between soma and axon ≈ axon hillock (physiological “trigger zone”).

Electrical Potentials: Resting, Local & Action

• Resting Potential: baseline, undisturbed state.
• Local Potential: small, localized voltage changes on soma/dendrites.
  • Can be excitatory (depolarizing) or inhibitory (hyperpolarizing).
  • Generated by chemically or mechanically gated channels.
• Action Potential: large, self-propagating electrical event triggered if local potential reaches threshold at the axon hillock.
  • Travels down axon → triggers neurotransmitter release in terminals → information processing in next neuron.

Ion Distribution & Membrane Potential

• Outside of neuron: high \text{Na}^+ (positively charged).
• Inside: high \text{K}^+ plus large, negatively charged proteins.
• Resulting electrical separation = membrane potential (potential energy difference).
  • Measurable with a voltmeter in millivolts (mV).
  • Resting value V_{rest} = -70\ \text{mV} (inside negative relative to outside).
• Forces driving ion motion if a channel opens:
  1. Electrical attraction (opposite charges attract).
  2. Diffusion (concentration gradient → move toward equilibrium).

Types of Ion Channels & Stimuli

1. Chemically-gated (ligand-gated)
   • Location: soma & dendrites.
   • Open/close when neurotransmitter or other ligand binds.
   • Mechanism for most synaptic input.
2. Voltage-gated
   • Location: axon & terminals.
   • Open when adjacent membrane potential changes ("neighbor triggers neighbor").
   • Responsible for AP propagation.
3. Mechanically-gated
   • Location: sensory dendritic endings (e.g., fingertips).
   • Open when membrane physically deforms (pressure, stretch).

Changes in Membrane Potential

• Depolarization: membrane becomes less negative (toward 0 or positive) as \text{Na}^+ enters.
• Repolarization: return toward resting value after depolarization.
• Hyperpolarization: membrane becomes more negative than rest (e.g., excessive \text{K}^+ efflux, vigorous Na⁺/K⁺ pump activity).
• Sodium–Potassium Pump (Na⁺/K⁺-ATPase)
  • Exchanges 3\ \text{Na}^+{out} for 2\ \text{K}^+{in} using ATP.
  • Helps restore ion gradients after AP; over-activity can hyperpolarize.

Threshold & Trigger Zone (Axon Hillock)

• Trigger zone must reach threshold voltage V_{threshold} \approx -55\ \text{mV}.
• Excitatory local potentials move toward threshold; inhibitory ones move away.
• Summation
  • Spatial: multiple synapses on different locations add.
  • Temporal: rapid, repeated input from the same synapse add.
• If combined effect pushes hillock to -55\ \text{mV} → voltage-gated \text{Na}^+ channels open → Action Potential initiated.

Action Potential Propagation

• AP = sequential opening/closing of voltage-gated \text{Na}^+/\text{K}^+ channels → “electrical wave.”
• Domino / stadium “wave” analogy:
  1. Neighboring patch depolarizes.
  2. You (next patch) sense voltage change → open your channels → later close (sit back down).
  3. Wave moves unidirectionally because regions just fired are in refractory state.

Continuous vs. Saltatory Conduction

Clinical Connection – Multiple Sclerosis (MS)

• Autoimmune destruction of oligodendrocytes (CNS myelin) ± Schwann cells (PNS).
• Etiology: suspected molecular mimicry after infection; immune system mistakes myelin proteins for pathogen.
• Pathology: loss of myelin → plaques / scars visible on MRI (bright white lesions in brain & spinal cord).
• Consequences of demyelination:
  • Slowed / blocked APs → sensory deficits.
  • Spasticity (sustained muscle contraction).
  • Loss of motor coordination → gait problems, wheelchair use.
  • Bladder & intestinal dysfunction (autonomic fiber failure).
  • Psychological impact (mood, cognition).
• Diagnosis toolbox:
  1. Neurological exam for focal deficits.
  2. Blood tests for inflammatory markers & possible infectious triggers.
  3. Lumbar puncture → cerebrospinal fluid with ↑ microglia & inhibitory proteins.
  4. MRI for plaques.
  5. Evoked potential test: electrically stimulate specific pathways; absent / delayed response = conduction failure.

Key Numbers, Equations & Terminology

• Resting potential: V_{rest} = -70\ \text{mV}.
• Threshold: V_{threshold} = -55\ \text{mV} at axon hillock.
• Na⁺/K⁺-ATPase stoichiometry: 3\ \text{Na}^+{out} : 2\ \text{K}^+{in} per ATP.
• Conduction velocities:
  • Continuous: \sim 1\ \text{m·s}^{-1}.
  • Saltatory: \sim 180\ \text{m·s}^{-1}.
• Polarization terms: depolarize (↑ toward 0), repolarize (return), hyperpolarize (↓ below rest).
• Channel types: chemically gated, voltage gated, mechanically gated.
• Trigger Zone = Axon Hillock (structural) / Threshold Zone (functional).
• Saltatory conduction Latin root: "saltare" = to leap.

Analogies & Real-World Connections

• Potential vs. kinetic energy: like water behind a dam; ion gradient stores energy.
• Sodium influx like opening floodgate; potassium efflux like draining reservoir.
• Stadium "wave" → visual for sequential opening/closing of channels.
• Empty stadium seats (myelin) → explains saltatory leaps.
• Fingertip pressure demo: pen tip activates mechanically gated channels → sensory AP.
• Weather forecast “potential” vs. neuron potential: both imply stored possibility but here quantified in volts.