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// ─── DESIGN TOKENS ────────────────────────────────────────────────────────────
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// ─── HELPERS ──────────────────────────────────────────────────────────────────
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// ════════════════════════════════════════════════════════════════════════════════
// SLIDES
// ════════════════════════════════════════════════════════════════════════════════

// ── 1. TITLE ─────────────────────────────────────────────────────────────────
titleSlide(
  "Neuromuscular Junction",
  "Anatomy · Physiology · Metabolism",
  C.navy
);

// ── 2. TABLE OF CONTENTS ─────────────────────────────────────────────────────
{
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    { n: "01", title: "Overview & Definition", color: C.blue },
    { n: "02", title: "Anatomy of the NMJ", color: C.teal },
    { n: "03", title: "Motor Unit & Motor End Plate", color: C.navy },
    { n: "04", title: "Acetylcholine: Synthesis & Storage", color: C.blue },
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    { n: "06", title: "Nicotinic Receptor Structure & Function", color: C.navy },
    { n: "07", title: "Endplate Potential & Action Potential", color: C.blue },
    { n: "08", title: "Excitation–Contraction Coupling", color: C.teal },
    { n: "09", title: "ACh Metabolism & Recycling", color: C.navy },
    { n: "10", title: "Quantal Release & Safety Factor", color: C.blue },
    { n: "11", title: "Summary & Clinical Relevance", color: C.teal },
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// ── 3. SECTION HEADER: ANATOMY ───────────────────────────────────────────────
sectionHeader("Section 1", "Anatomy of the Neuromuscular Junction", C.blue);

// ── 4. OVERVIEW ──────────────────────────────────────────────────────────────
contentSlide("Overview: What is the NMJ?", [
  { text: "The neuromuscular junction (NMJ) is the specialized chemical synapse between a motor neuron axon terminal and a skeletal muscle fiber.", bold: true },
  { text: "" },
  { text: "Key concept: Converts an electrical nerve signal into a chemical signal, which then re-initiates an electrical signal in the muscle." },
  { text: "" },
  { text: "Location: Where the axon of a lower motor neuron terminates on the sarcolemma of a skeletal muscle fiber." },
  { text: "" },
  { text: "Also called:", bold: true },
  { text: "Motor end plate (the muscle membrane side of the junction)", sub: true },
  { text: "Myoneural junction", sub: true },
  { text: "" },
  { text: "Neurotransmitter: Acetylcholine (ACh) – released from presynaptic terminal, acts on postsynaptic nicotinic receptors (NM type)." },
], "Source: Ganong's Review of Medical Physiology, 26e");

// ── 5. ANATOMY COMPONENTS ────────────────────────────────────────────────────
twoColSlide(
  "Structural Components of the NMJ",
  "Presynaptic (Nerve Terminal)",
  [
    { text: "Axon loses myelin sheath as it approaches muscle", bold: false },
    { text: "Divides into terminal boutons (bulb-like endings)" },
    { text: "Active zones: specialized membrane sites for ACh vesicle fusion" },
    { text: "Mitochondria: supply ATP for ACh synthesis" },
    { text: "Synaptic vesicles: ~10,000 ACh molecules each (one quantum)" },
    { text: "Voltage-gated Ca²⁺ channels: trigger exocytosis upon depolarization" },
    { text: "SNARE proteins (VAMP/synaptobrevin): mediate vesicle docking & fusion" },
    { text: "Synaptotagmin: calcium sensor on vesicle membrane" },
  ],
  "Postsynaptic (Motor End Plate)",
  [
    { text: "Thickened region of sarcolemma = motor end plate", bold: false },
    { text: "Junctional folds: deep infoldings that increase surface area" },
    { text: "Nicotinic ACh receptors (nAChRs): clustered at tops of junctional folds" },
    { text: "Acetylcholinesterase (AChE): enzyme in the synaptic cleft & folds" },
    { text: "Na⁺/K⁺ channels: opened by ACh binding → endplate potential" },
    { text: "Voltage-gated Na⁺ channels: dense at base of junctional folds" },
    { text: "Each endplate receives input from only ONE nerve fiber" },
  ],
  C.lightBlue,
  C.lightTeal
);

// ── 6. SYNAPTIC CLEFT ────────────────────────────────────────────────────────
contentSlide("The Synaptic Cleft", [
  { text: "A gap of ~50–100 nm separates the presynaptic nerve terminal from the postsynaptic motor end plate.", bold: true },
  { text: "" },
  { text: "Contents of the synaptic cleft:" },
  { text: "Basal lamina (extracellular matrix) running through the cleft", sub: true },
  { text: "Acetylcholinesterase (AChE) – anchored to basal lamina, rapidly destroys ACh", sub: true },
  { text: "Released ACh molecules diffuse across the 50 nm gap in microseconds", sub: true },
  { text: "" },
  { text: "Junctional folds amplify the signal:" },
  { text: "Increase the surface area of the motor end plate ~10-fold", sub: true },
  { text: "nAChRs concentrated at the tops/crests of the folds (~10,000 receptors/µm²)", sub: true },
  { text: "Voltage-gated Na⁺ channels concentrated at the depths of the folds", sub: true },
  { text: "" },
  { text: "This spatial arrangement ensures maximal receptor activation and rapid signal termination after ACh is released." },
], "Source: Miller's Anesthesia, 10e");

// ── 7. MOTOR UNIT ─────────────────────────────────────────────────────────────
contentSlide("Motor Unit & Innervation", [
  { text: "Motor Unit = One alpha motor neuron + all muscle fibers it innervates", bold: true },
  { text: "" },
  { text: "Innervation ratio varies with function:" },
  { text: "Fine motor muscles (e.g., extraocular): 1 neuron : 3–6 fibers", sub: true },
  { text: "Power muscles (e.g., gastrocnemius): 1 neuron : 1,000–2,000 fibers", sub: true },
  { text: "" },
  { text: "Each skeletal muscle fiber receives innervation from exactly ONE motor neuron." },
  { text: "" },
  { text: "The motor neuron axon branches near the muscle, sending a terminal bouton to each fiber it innervates." },
  { text: "" },
  { text: "Acetylcholine receptor clustering at the endplate is maintained by agrin (released from nerve terminal) → activates MuSK receptor on muscle → activates rapsyn → clusters nAChRs." },
  { text: "" },
  { text: "Loss of innervation → spread of nAChRs across entire muscle surface (denervation supersensitivity)." },
], "Source: Ganong's Review of Medical Physiology, 26e · Miller's Anesthesia, 10e");

// ── 8. SECTION: PHYSIOLOGY ───────────────────────────────────────────────────
sectionHeader("Section 2", "Physiology of Neuromuscular Transmission", C.teal);

// ── 9. ACH SYNTHESIS ─────────────────────────────────────────────────────────
contentSlide("Acetylcholine (ACh): Synthesis", [
  { text: "ACh is the neurotransmitter at the NMJ. It is synthesized in the nerve terminal cytoplasm.", bold: true },
  { text: "" },
  { text: "Substrates:" },
  { text: "Choline – transported into the nerve terminal from extracellular fluid by high-affinity choline transporter (ChT1)", sub: true },
  { text: "Acetyl-CoA – derived from mitochondrial metabolism of pyruvate (from glucose)", sub: true },
  { text: "" },
  { text: "Reaction:" },
  { text: "Choline + Acetyl-CoA  →  Acetylcholine + CoA", bold: true },
  { text: "Enzyme: Choline acetyltransferase (ChAT)", sub: true },
  { text: "" },
  { text: "After synthesis, ACh is packaged into synaptic vesicles by vesicular acetylcholine transporter (VAChT)." },
  { text: "" },
  { text: "Each vesicle contains ~10,000 ACh molecules (one quantum)." },
  { text: "" },
  { text: "All synthesis machinery (ChAT, VAChT) is made in the motor neuron cell body and transported by axonal transport to the nerve terminal." },
], "Source: Miller's Anesthesia, 10e · Basic Medical Biochemistry, 6e");

// ── 10. VESICLE POOLS ────────────────────────────────────────────────────────
twoColSlide(
  "ACh Storage: Vesicle Pools",
  "Readily Releasable Pool (RRP)",
  [
    { text: "Vesicles docked at active zones", bold: true },
    { text: "Immediately available for release" },
    { text: "~1,000 vesicles at the active zone" },
    { text: "SNARE complex pre-formed" },
    { text: "Released by first few nerve stimuli" },
    { text: "" },
    { text: "SNARE Proteins involved:", bold: true },
    { text: "VAMP (synaptobrevin) – on vesicle" },
    { text: "Syntaxin – on nerve terminal membrane" },
    { text: "SNAP-25 – on nerve terminal membrane" },
    { text: "Synaptotagmin – Ca²⁺ sensor, triggers fusion" },
  ],
  "Mobilization / Reserve Pool",
  [
    { text: "Vesicles held by cytoskeletal scaffold", bold: true },
    { text: "Released during sustained stimulation" },
    { text: "Synapsin I phosphorylation mobilizes vesicles" },
    { text: "Important for maintaining transmission during tetanic stimulation" },
    { text: "" },
    { text: "Recycling after exocytosis:", bold: true },
    { text: "Endocytosis of membrane (clathrin-mediated)" },
    { text: "Re-acidification of vesicle lumen" },
    { text: "Reload with ACh via VAChT" },
    { text: "Synaptophysin: major vesicle membrane glycoprotein" },
  ],
  C.lightBlue,
  C.lightTeal
);

// ── 11. STEP-BY-STEP TRANSMISSION ────────────────────────────────────────────
stepSlide(
  "Neuromuscular Transmission: Step-by-Step",
  [
    { title: "1. Action Potential Arrives", desc: "Nerve AP travels down motor axon → reaches terminal bouton → membrane depolarizes." },
    { title: "2. Ca²⁺ Channel Opens", desc: "Depolarization opens voltage-gated Ca²⁺ channels (P/Q-type) on nerve terminal membrane." },
    { title: "3. Ca²⁺ Influx", desc: "Ca²⁺ rushes into nerve terminal down its concentration gradient. [Ca²⁺] rises ~100-fold locally." },
    { title: "4. Vesicle Fusion (Exocytosis)", desc: "Ca²⁺ binds synaptotagmin → SNARE complex zipps → vesicle fuses with membrane → ACh released into cleft." },
    { title: "5. ACh Diffuses Across Cleft", desc: "ACh crosses the ~50–100 nm synaptic cleft in microseconds." },
    { title: "6. ACh Binds nAChR", desc: "2 ACh molecules bind both α-subunits of the nicotinic receptor → channel opens." },
    { title: "7. Endplate Potential (EPP)", desc: "Na⁺ influx (and K⁺ efflux) through nAChR → local depolarization = endplate potential." },
    { title: "8. Action Potential Generated", desc: "EPP depolarizes adjacent sarcolemma → voltage-gated Na⁺ channels fire → muscle AP propagates." },
  ],
  "Each step can be modulated by drugs (neuromuscular blockers, anticholinesterases, toxins). Source: Ganong's 26e · Miller's Anesthesia 10e"
);

// ── 12. NICOTINIC RECEPTOR ───────────────────────────────────────────────────
contentSlide("Nicotinic ACh Receptor (nAChR) Structure", [
  { text: "Pentameric ligand-gated ion channel (ionotropic receptor) – belongs to Cys-loop receptor superfamily.", bold: true },
  { text: "" },
  { text: "Mature muscle nAChR subunit composition:", bold: false },
  { text: "2α  +  1β  +  1δ  +  1ε   (adult/junctional type)", sub: true },
  { text: "2α  +  1β  +  1δ  +  1γ   (fetal/extrajunctional type)", sub: true },
  { text: "" },
  { text: "Two ACh binding sites: located at the interfaces of each α-subunit with its neighboring δ and ε (or γ) subunit." },
  { text: "" },
  { text: "Activation requirement: BOTH α-subunits must be simultaneously occupied by ACh." },
  { text: "" },
  { text: "Channel properties when open:" },
  { text: "Non-selective cation channel – permeable to Na⁺, K⁺, and Ca²⁺", sub: true },
  { text: "Net effect: Na⁺ influx > K⁺ efflux → depolarization", sub: true },
  { text: "Each channel passes ~4 pA; ~500,000 channels open per nerve stimulus", sub: true },
  { text: "" },
  { text: "Channel closes when one or both ACh molecules dissociate. AChE removes ACh from the cleft within ~1 ms." },
], "Source: Miller's Anesthesia, 10e · Katzung Pharmacology, 16e");

// ── 13. TABLE – RECEPTOR TYPES ───────────────────────────────────────────────
tableSlide(
  "Junctional vs Extrajunctional nAChRs",
  ["Property", "Junctional (Mature)", "Extrajunctional (Fetal)"],
  [
    ["Subunit composition", "2α₁ + β₁ + δ + ε", "2α₁ + β₁ + δ + γ"],
    ["Location", "Concentrated at endplate", "Spread across whole muscle"],
    ["Channel open time", "~1 ms (brief)", "~5 ms (prolonged)"],
    ["Conductance", "~60 pS", "~40 pS"],
    ["Sensitivity to succinylcholine", "Normal", "Increased (K⁺ efflux risk)"],
    ["Present in adults", "Yes (normal)", "Only if denervated/immobilized"],
    ["Clinical relevance", "Target for NDMRs", "Dangerous hyperkalemia with suxamethonium"],
  ],
  "NDMR = Non-depolarizing muscle relaxant. Source: Miller's Anesthesia, 10e"
);

// ── 14. ENDPLATE POTENTIAL ───────────────────────────────────────────────────
contentSlide("Endplate Potential (EPP) & Safety Factor", [
  { text: "EPP is the graded depolarization at the motor endplate produced by ACh-induced nAChR activation.", bold: true },
  { text: "" },
  { text: "Magnitude of EPP:" },
  { text: "Normal EPP amplitude: ~70–80 mV (well above the ~−55 mV threshold for AP generation)", sub: true },
  { text: "Each nerve impulse normally releases ~200–300 quanta of ACh", sub: true },
  { text: "Only ~25–30 quanta are needed to trigger a muscle AP → large safety margin", sub: true },
  { text: "" },
  { text: "Safety Factor:", bold: true },
  { text: "Ratio of actual EPP to threshold EPP ≈ 3–5× (very high safety margin)", sub: true },
  { text: "This ensures reliable neuromuscular transmission under most physiological conditions", sub: true },
  { text: "Safety factor is REDUCED in: myasthenia gravis, LEMS, aminoglycoside antibiotics", sub: true },
  { text: "" },
  { text: "The EPP is NOT an action potential – it is a local graded potential. It reaches threshold and triggers flanking voltage-gated Na⁺ channels → full muscle AP." },
  { text: "" },
  { text: "Action potentials propagate bidirectionally along the muscle fiber, entering T-tubules." },
], "Source: Ganong's 26e · Miller's Anesthesia, 10e");

// ── 15. SECTION: METABOLISM ──────────────────────────────────────────────────
sectionHeader("Section 3", "Metabolism at the NMJ", C.navy);

// ── 16. EXCITATION–CONTRACTION COUPLING ──────────────────────────────────────
stepSlide(
  "Excitation–Contraction (E–C) Coupling",
  [
    { title: "AP into T-tubules", desc: "Muscle AP propagates along sarcolemma and enters transverse tubule (T-tubule) system." },
    { title: "DHPR Activation", desc: "Dihydropyridine receptor (DHPR) in T-tubule membrane senses voltage change → conformational change." },
    { title: "RyR Activation", desc: "DHPR physically couples to and activates ryanodine receptor (RyR1) on sarcoplasmic reticulum (SR) membrane." },
    { title: "Ca²⁺ Release from SR", desc: "RyR1 opens → Ca²⁺ floods from SR into sarcoplasm (rises from 10⁻⁷ to 10⁻⁵ M)." },
    { title: "Troponin C Binding", desc: "Ca²⁺ binds troponin C → conformational change moves tropomyosin → exposes myosin-binding sites on actin." },
    { title: "Cross-bridge Cycling", desc: "Myosin heads bind actin → power stroke (pivoting) → sarcomere shortens → muscle contracts. Requires ATP." },
    { title: "Relaxation", desc: "SR Ca²⁺-ATPase (SERCA) pumps Ca²⁺ back into SR against gradient → Ca²⁺ falls → troponin releases → tropomyosin covers actin → relaxation." },
  ],
  "DHPR = dihydropyridine receptor; RyR1 = ryanodine receptor type 1; SERCA = sarcoplasmic/endoplasmic reticulum Ca²⁺-ATPase. Source: Basic Medical Biochemistry, 6e"
);

// ── 17. ACHE METABOLISM ──────────────────────────────────────────────────────
contentSlide("ACh Metabolism: Acetylcholinesterase (AChE)", [
  { text: "Termination of ACh action is achieved primarily by enzymatic hydrolysis by acetylcholinesterase (AChE).", bold: true },
  { text: "" },
  { text: "Location of AChE:" },
  { text: "Anchored to the basal lamina in the synaptic cleft", sub: true },
  { text: "Also on the junctional folds of the motor end plate", sub: true },
  { text: "" },
  { text: "Reaction:" },
  { text: "ACh  +  H₂O  →  Choline  +  Acetate  (catalyzed by AChE)", bold: true },
  { text: "" },
  { text: "Speed: One of the fastest enzymes known – hydrolyzes ACh in <1 ms." },
  { text: "" },
  { text: "Fate of products:" },
  { text: "Choline: ~50% is recycled back into the nerve terminal via high-affinity Na⁺-dependent choline transporter (rate-limiting step for new ACh synthesis)", sub: true },
  { text: "Acetate: diffuses away into plasma", sub: true },
  { text: "" },
  { text: "Clinical: AChE inhibitors (neostigmine, pyridostigmine) block this reaction → ACh accumulates → enhanced and prolonged EPP → reversal of NDMR block." },
], "Source: Ganong's 26e · Goodman & Gilman's, Guyton & Hall Physiology");

// ── 18. ACH RECYCLING CYCLE ──────────────────────────────────────────────────
diagramSlide(
  "ACh Synthesis–Release–Hydrolysis Cycle",
  [
    { text: "Glucose → Pyruvate → Acetyl-CoA (mitochondria)", color: C.lightTeal, borderColor: C.teal, bold: false },
    { text: "Choline Uptake (ChT1 transporter)", color: C.lightBlue, borderColor: C.blue },
    { text: "ACh Synthesis\nCholine + Acetyl-CoA\n→ ACh (ChAT enzyme)", color: C.accentLight, borderColor: C.accent, bold: true },
    { text: "Packaging into vesicles (VAChT)", color: C.lightBlue, borderColor: C.blue },
    { text: "Nerve AP → Ca²⁺ influx", color: C.lightTeal, borderColor: C.teal },
    { text: "Exocytosis of ACh\n(SNARE complex)", color: C.accentLight, borderColor: C.accent, bold: true },
    { text: "ACh binds nAChR\n→ Muscle contraction", color: C.lightBlue, borderColor: C.blue, bold: true },
    { text: "AChE hydrolyzes ACh\n→ Choline + Acetate", color: C.lightTeal, borderColor: C.teal },
  ],
  "The cycle is continuous: choline is recycled back from the cleft to re-enter synthesis. Rate-limiting step: choline uptake."
);

// ── 19. QUANTAL RELEASE & CALCIUM ────────────────────────────────────────────
contentSlide("Quantal Release & Calcium Dependence", [
  { text: "ACh is released in discrete packets called quanta. Each quantum = contents of one synaptic vesicle (~10,000 ACh molecules).", bold: true },
  { text: "" },
  { text: "Spontaneous release:" },
  { text: "Even without a nerve impulse, individual vesicles randomly fuse → produce miniature endplate potentials (MEPPs)", sub: true },
  { text: "MEPPs are ~0.5 mV each (sub-threshold) – markers of quantal release", sub: true },
  { text: "" },
  { text: "Evoked release (during AP):" },
  { text: "~200–300 quanta released simultaneously per AP", sub: true },
  { text: "Total EPP = sum of individual quantal contributions", sub: true },
  { text: "" },
  { text: "Critical role of Ca²⁺:" },
  { text: "If no Ca²⁺ in extracellular fluid → NO ACh release even with normal depolarization", sub: true },
  { text: "Doubling extracellular Ca²⁺ → 16-fold increase in quantal content released", sub: true },
  { text: "Mg²⁺ competes with Ca²⁺ and reduces quantal release", sub: true },
  { text: "" },
  { text: "Posttetanic potentiation (PTP): Ca²⁺ accumulates in terminal after tetanic stimulation → temporarily increased ACh release → transient reversal of neuromuscular block." },
], "Source: Miller's Anesthesia, 10e");

// ── 20. ENERGY METABOLISM AT NMJ ─────────────────────────────────────────────
contentSlide("Energy Metabolism at the NMJ", [
  { text: "The NMJ is metabolically highly active and depends on continuous ATP supply.", bold: true },
  { text: "" },
  { text: "ATP is required for:" },
  { text: "ACh synthesis: formation of Acetyl-CoA from glucose metabolism", sub: true },
  { text: "Vesicle loading: VAChT transporter is H⁺-ATPase driven (proton gradient)", sub: true },
  { text: "Axonal transport: kinesin/dynein motors transport vesicle precursors to terminal", sub: true },
  { text: "Vesicle recycling: clathrin-mediated endocytosis requires ATP", sub: true },
  { text: "SERCA pump: ATP needed to return Ca²⁺ to SR after contraction", sub: true },
  { text: "Na⁺/K⁺-ATPase: restores resting membrane potential after each AP", sub: true },
  { text: "" },
  { text: "Key mitochondrial role: Motor nerve terminals are rich in mitochondria, providing ATP and acetyl-CoA for sustained neurotransmission." },
  { text: "" },
  { text: "Ischemia or metabolic failure → rapid decline in ACh synthesis and vesicle recycling → neuromuscular failure." },
], "Source: Miller's Anesthesia, 10e · Basic Medical Biochemistry, 6e");

// ── 21. SUMMARY TABLE ────────────────────────────────────────────────────────
tableSlide(
  "NMJ Molecules: Roles at a Glance",
  ["Molecule", "Location", "Role"],
  [
    ["Choline acetyltransferase (ChAT)", "Nerve terminal cytoplasm", "Synthesizes ACh from choline + acetyl-CoA"],
    ["VAChT", "Vesicle membrane", "Loads ACh into synaptic vesicles (H⁺ gradient driven)"],
    ["Synaptotagmin", "Vesicle membrane", "Ca²⁺ sensor – triggers SNARE-mediated exocytosis"],
    ["VAMP / Synaptobrevin", "Vesicle membrane (v-SNARE)", "Docks vesicle to active zone; drives fusion"],
    ["SNAP-25 + Syntaxin", "Nerve terminal membrane (t-SNARE)", "Partner proteins completing SNARE complex"],
    ["nAChR (NM)", "Motor end plate (junctional folds)", "Ligand-gated Na⁺/K⁺ channel; generates EPP"],
    ["Acetylcholinesterase (AChE)", "Synaptic cleft / basal lamina", "Hydrolyzes ACh → choline + acetate (<1 ms)"],
    ["ChT1 (high-affinity)", "Nerve terminal membrane", "Recycles choline back into terminal (rate-limiting)"],
    ["Ryanodine receptor (RyR1)", "SR membrane", "Ca²⁺ release channel (opens during E–C coupling)"],
    ["SERCA pump", "SR membrane", "Pumps Ca²⁺ back into SR; enables relaxation"],
  ],
  "ACh = acetylcholine; SR = sarcoplasmic reticulum; EPP = endplate potential"
);

// ── 22. KEY POINTS ───────────────────────────────────────────────────────────
keyPointsSlide("Key Takeaways", [
  { icon: "1", title: "Chemical Synapse", text: "NMJ converts electrical nerve signals to chemical (ACh), then back to electrical (EPP → muscle AP)" },
  { icon: "2", title: "Ca²⁺ is the Key Trigger", text: "Ca²⁺ influx through P/Q-type channels is absolutely required for ACh exocytosis" },
  { icon: "3", title: "Quantal Release", text: "ACh released in quanta (~10,000 molecules/vesicle); EPP = sum of hundreds of simultaneous quanta" },
  { icon: "4", title: "High Safety Factor", text: "3–5× more ACh released than needed to fire muscle AP; ensures reliable transmission" },
  { icon: "5", title: "nAChR Pentamer", text: "Both α-subunits must bind ACh simultaneously to open the cation channel" },
  { icon: "6", title: "Rapid Termination", text: "AChE hydrolyzes ACh in <1 ms; choline is recycled back (rate-limiting for new synthesis)" },
]);

// ── 23. CLINICAL RELEVANCE ───────────────────────────────────────────────────
contentSlide("Clinical Relevance of NMJ Physiology", [
  { text: "Understanding NMJ physiology underlies many clinical scenarios:", bold: true },
  { text: "" },
  { text: "Myasthenia Gravis: autoantibodies against nAChRs → reduced EPP → fatigable weakness; treated with AChE inhibitors (pyridostigmine)" },
  { text: "" },
  { text: "Lambert-Eaton Myasthenic Syndrome (LEMS): autoantibodies against presynaptic Ca²⁺ channels → reduced ACh release → proximal weakness" },
  { text: "" },
  { text: "Neuromuscular Blocking Drugs (NMBDs):" },
  { text: "Depolarizing: Succinylcholine mimics ACh → prolonged depolarization → fasciculations then flaccid paralysis", sub: true },
  { text: "Non-depolarizing: Vecuronium, rocuronium compete with ACh at nAChR → prevent channel opening → reversed by AChE inhibitors or sugammadex", sub: true },
  { text: "" },
  { text: "Organophosphate poisoning: irreversible AChE inhibition → ACh accumulates → continuous muscle stimulation → paralysis" },
  { text: "" },
  { text: "Botulinum toxin: cleaves SNARE proteins (SNAP-25) → prevents ACh vesicle fusion → flaccid paralysis" },
], "Source: Katzung Pharmacology 16e · Miller's Anesthesia 10e · Goodman & Gilman's");

// ── 24. END SLIDE ─────────────────────────────────────────────────────────────
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// ─── SAVE ─────────────────────────────────────────────────────────────────────
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