Action Potentials
Neurons maintain a resting membrane potential of approximately -70 mV (inside negative) due to the K+ leak channels and Na+/K+-ATPase pump. An action potential occurs when a stimulus depolarizes the membrane to threshold (~-55 mV).
| Phase | Ion Movement | Key Feature |
|---|---|---|
| Resting (-70 mV) | K+ leaks out; Na+ leaks in (small) | Na+/K+ pump maintains gradient (3 Na+ out, 2 K+ in) |
| Depolarization | Voltage-gated Na+ channels OPEN → Na+ rushes in | All-or-none response; propagates along axon |
| Repolarization | Na+ channels close (inactivate); K+ channels open → K+ rushes out | Absolute refractory period — no new AP possible |
| Hyperpolarization (undershoot) | K+ channels slow to close → extra K+ out | Relative refractory period — higher threshold |
⭐ Conduction VelocityLarger diameter axons = faster conduction. Myelinated axons (saltatory conduction from node to node) are fastest. Type A-alpha fibers: proprioception, motor (fastest). Type C fibers: pain, temperature, autonomic (slowest, unmyelinated).
Synaptic Transmission
Chemical synapse: Action potential → voltage-gated Ca2+ channels open in presynaptic terminal → Ca2+ influx → vesicle fusion → neurotransmitter release into synaptic cleft → binds postsynaptic receptors → EPSP or IPSP. Neurotransmitter removed by reuptake, enzymatic degradation, or diffusion.
🩹 Lambert-Eaton vs Myasthenia GravisMyasthenia gravis: autoantibodies against postsynaptic ACh receptors → fatigable weakness; improves with rest; ocular symptoms first. Lambert-Eaton: autoantibodies against presynaptic voltage-gated Ca2+ channels → weakness that IMPROVES with repeated stimulation; associated with small cell lung cancer.
Key Neurotransmitters
| Neurotransmitter | Synthesized From | Key Pathways | Clinical Relevance |
|---|---|---|---|
| Acetylcholine (ACh) | Choline + acetyl-CoA (choline acetyltransferase) | NMJ, parasympathetic, basal ganglia | Deficient in Alzheimer's (nucleus basalis); myasthenia gravis |
| Dopamine | Tyrosine → DOPA → dopamine (DOPA decarboxylase) | Nigrostriatal (movement), mesolimbic (reward), tuberoinfundibular | Low: Parkinson's; High: schizophrenia; blocks tuberoinfundibular → hyperprolactinemia with antipsychotics |
| Norepinephrine | Dopamine → NE (dopamine beta-hydroxylase) | Locus coeruleus → cortex, sympathetic NS | Low: depression; SNRIs and TCAs block reuptake |
| Serotonin (5-HT) | Tryptophan → 5-HTP → 5-HT | Raphe nuclei → cortex, limbic system, GI tract (90%) | Low: depression, anxiety; SSRIs/SNRIs target; carcinoid tumor produces excess |
| GABA | Glutamate → GABA (GAD) | Primary CNS inhibitory NT | Target of benzodiazepines, barbiturates, alcohol; low in anxiety, seizures |
| Glutamate | Alpha-ketoglutarate | Primary CNS excitatory NT; NMDA and AMPA receptors | Excess: excitotoxicity in stroke, TBI; memantine blocks NMDA in Alzheimer's |
Autonomic Nervous System
| Feature | Sympathetic | Parasympathetic |
|---|---|---|
| Origin | Thoracolumbar (T1-L2) | Craniosacral (CN III,VII,IX,X; S2-S4) |
| Pre/postganglionic | Short pre / long post | Long pre / short post (ganglia near organ) |
| Preganglionic NT | ACh (nicotinic receptor) | ACh (nicotinic receptor) |
| Postganglionic NT | Norepinephrine (adrenergic receptors); except sweat (ACh) | ACh (muscarinic receptors) |
| Effect | "Fight or flight": tachycardia, mydriasis, bronchodilation, decreased GI, increased BP | "Rest and digest": bradycardia, miosis, bronchoconstriction, increased GI, decreased BP |
🧐 Muscarinic Receptor Effects (DUMBELS)Diarrhea, Urination, Miosis, Bradycardia, Emesis, Lacrimation, Salivation. Used for cholinergic toxicity (organophosphate poisoning). Treatment: atropine (muscarinic antagonist).
Pain Physiology
Pain transduction: nociceptors → A-delta fibers (sharp, fast pain) and C fibers (dull, slow, burning) → dorsal horn → spinothalamic tract → thalamus → cortex. Modulated at dorsal horn by descending inhibitory pathways (NE, serotonin, endorphins).
⭐ Gate Control TheoryNon-painful stimuli (touch, pressure via A-beta fibers) can inhibit pain signals at the dorsal horn — "closes the gate." Clinical application: TENS units, massage, rubbing an injury. Descending pathways (from PAG) release endorphins/enkephalins → inhibit pain at dorsal horn.
Clinical Pearls
🩹 Sleep Stages and PhysiologyNREM stages 1-3 (light to deep sleep, delta waves in stage 3). REM sleep: dreaming, paradoxical eye movements, muscle atonia, sympathetic activation. Sleep cycle ~90 min. REM decreases with age. Suppressed by: alcohol, benzodiazepines, opioids.
⭐ Hypothalamic-Pituitary AxesCRH (hypothalamus) → ACTH (anterior pituitary) → cortisol (adrenal cortex) — negative feedback. TRH → TSH → T3/T4. GnRH (pulsatile) → LH/FSH → sex steroids. GHRH → GH → IGF-1. ADH and oxytocin are posterior pituitary (made in hypothalamus, stored/released from posterior pituitary).