Neuron Action Potential (HY)

1. Resting Membrane Potential
   • Membrane is more permeable to K+ than Na+ at rest.
   • Voltage-gated Na+ and K+ channels are closed.
2. Membrane Depolarization
   • Na+ activation gate opens → Na+ flows inward.
3. Membrane Repolarization
   • Na+ inactivation gate closes at peak potential, stopping Na+ inflow.
   • K+ activation gate opens → K+ flows outward.
4. Membrane Hyperpolarization
   • K+ activation gates are slow to close, causing excess K+ efflux and a brief period of hyperpolarization.
   • Voltage-gated Na+ channels switch back to the resting state.
   • Na+/K+ pump restores ion concentrations.

Neurotransmitters

Neurotransmitter Changes with Disease

• UWT of neurotransmitter system in CNS

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Anatomical correlation

• Nucleus accumbens → involved in motivation and reward pathways.
• Locus ceruleus is present in posterior rostral pons near lateral floor of 4th ventricle.
• Explanatory picture </aside>

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GABA vs Glutamate

• Glutamate
  • Main excitatory neurotransmitter of the brain.
  • Act by binding to NMDA receptors and allow the influx of Na and Ca ions → Activation of the neuron.
• GABA
  • Main inhibitory neurotransmitter of the brain
  • Act by binding to GABA$_A$ receptors and allow the influx of Cl channels (site of action of Barbiturates and BZs) </aside>

https://youtu.be/wP9QD-5FL5U?si=-BIZtwmlZutG-z-S

Glutamate excitotoxicity cascade

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Glutamate-induced excitotoxicity has emerged as a key player in the outward propagation of injury.

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Pathophysiology

• Within minutes of focal brain injury (stroke , Alzheimer’s), neurons depolarize because of ATP depletion→ exocytosis of glutamate-containing vesicles→ sudden, massive surge of glutamate into the extracellular space → NMDA receptor is activated→ calcium influx into the cell → causing depolarization (and additional glutamate release) from neurons adjacent to the infarct core→ Rapid calcium overload overwhelms the cell ability to overcome (Ca fluctuations normally buffered by mitochondria and ER)→ mitochondrial dysfunction, free radical formation, and calcium-dependent protease activation→ The neuron ultimately dies, ruptures, and releases more glutamate.

Clinical relevance

• Memantine is used in Alzheimer’s disease as it breaks this cycle by inhibiting NMDA receptors.

Synaptic transmission

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Synaptic transmission is the process of communication between nerve cells.

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https://youtu.be/NUIGGvzLd3g?si=rYjPOvslCYUzxnRC

Types of arrangements

1. One-to-one synapses
   • An action potential in the presynaptic element produces an action potential in the postsynaptic element.