NMJ Summery and MCQS

NEUROMUSCULAR JUNCTION (NMJ) – Summary for Easy Memorization Definition • The neuromuscular junction is the junction between the terminal branch of a motor nerve fiber and a skeletal muscle fiber. • It allows the transfer of nerve impulses to muscles, initiating contraction. Structure of NMJ 1. Motor Neuron & Muscle Fiber o Skeletal muscle fibers are innervated by large myelinated motor nerves from the anterior horn of the spinal cord. o Each nerve fiber may stimulate 3 to 100s of muscle fibers. 2. Axon Terminal o Terminal part of the nerve (axon) is called the axon terminal. o Loses myelin sheath near muscle, exposing the axis cylinder. o Expands to form a bulb-like structure: the motor endplate. 3. Motor Endplate o Highly folded area on the muscle membrane where the nerve terminals sit. o Covered by Schwann cells for insulation. 4. Synaptic Trough (Gutter) o The invaginated depression on the muscle membrane where the motor endplate lies. 5. Synaptic Cleft o Space (20–30 nm wide) between nerve terminal and muscle fiber. o Contains basal lamina and the enzyme acetylcholinesterase (AchE). 6. Subneural Clefts o Folds in the postsynaptic membrane (muscle side) to increase surface area. o Contain nicotinic acetylcholine receptors. Acetylcholine (ACh) • A neurotransmitter synthesized in the axon terminal from acetyl CoA + choline via choline acetyltransferase (ChAT). • Stored in synaptic vesicles (~300,000 vesicles per terminal). • Released during nerve impulse and binds to receptors on the muscle membrane. Neuromuscular Transmission – 5 Events 1. Release of Acetylcholine o Action potential opens voltage-gated calcium channels. o Calcium influx causes vesicles to fuse with membrane and release ACh (via exocytosis). 2. Action of Acetylcholine o ACh binds to nicotinic receptors on the postsynaptic membrane. o Opens ligand-gated sodium channels, allowing Na⁺ influx, changing membrane potential. 3. Endplate Potential (EPP) o Local depolarization caused by sodium influx. o Changes resting membrane potential (–90 mV) toward threshold. 4. Miniature Endplate Potential (MEPP) o Caused by random release of a small amount of ACh. o Weak, ~0.5 mV, not enough to cause contraction. 5. Destruction of ACh o Acetylcholinesterase breaks ACh into acetate and choline within 1 ms. o Prevents continuous stimulation of muscle. Reuptake & Recycling • Choline re-enters the presynaptic terminal by reuptake. • Used again to resynthesize acetylcholine. Neuromuscular Blockers (Inhibit NMJ) Used in anesthesia to relax muscles and cause paralysis: • Curare • Bungarotoxin (snake venom) • Succinylcholine • Carbamylcholine • Botulinum toxin Neuromuscular Stimulants (Enhance NMJ) Inhibit acetylcholinesterase → ACh not broken down → prolonged muscle contraction: • Neostigmine • Physostigmine • Diisopropyl fluorophosphate Mnemonic to Remember the 5 Events of NMJ Transmission: "RAPED" R – Release of ACh A – Action of ACh P – Potential (Endplate) E – Endplate (Miniature) D – Destruction of ACh Structure and Anatomy 1. The neuromuscular junction is the junction between: o A) Two muscle fibers o B) Two nerve fibers o C) A motor nerve terminal and a muscle fiber o D) Two axon terminals 2. The terminal portion of the motor nerve that innervates a muscle fiber is called: o A) Synaptic cleft o B) Subneural cleft o C) Axon terminal o D) Motor root 3. The motor endplate is: o A) Part of the nerve cell body o B) Specialized area of the muscle membrane under the axon terminal o C) Schwann cell layer o D) Node of Ranvier 4. The space between the nerve terminal and muscle membrane is called: o A) Myelin sheath o B) Synaptic cleft o C) Endoneurium o D) Sarcomere gap 5. The enzyme acetylcholinesterase is located in: o A) Synaptic vesicle o B) Axon hillock o C) Basal lamina of synaptic cleft o D) Subneural cleft 6. Subneural clefts serve to: o A) Store calcium o B) Increase surface area for receptors o C) Break down neurotransmitters o D) Transport ATP Neurotransmission Events 7. Which ion triggers release of acetylcholine from the axon terminal? o A) Sodium o B) Potassium o C) Calcium o D) Chloride 8. The binding of ACh to nicotinic receptors causes: o A) Hyperpolarization o B) Potassium efflux o C) Sodium influx o D) Closure of calcium channels 9. The normal resting membrane potential at NMJ is: o A) +40 mV o B) –60 mV o C) –90 mV o D) –110 mV 10. Endplate potential is generated due to: • A) Efflux of chloride • B) Influx of sodium • C) Outflux of calcium • D) Influx of potassium 11. Miniature endplate potential (MEPP) is: • A) A pathological event • B) A small depolarization due to spontaneous release of ACh • C) Caused by action potential • D) Always leads to contraction 12. The action of ACh is terminated by: • A) Passive diffusion • B) Enzymatic breakdown by acetylcholinesterase • C) Active transport • D) Storage in synaptic cleft 13. The product reabsorbed by the presynaptic terminal for ACh resynthesis is: • A) Acetate • B) Choline • C) Glucose • D) Acetyl-CoA 14. The full effect of ACh on the muscle fiber lasts approximately: • A) 1 second • B) 100 ms • C) 1 millisecond • D) 10 milliseconds Acetylcholine (ACh) and its Metabolism 15. Acetylcholine is synthesized from: • A) Glucose and acetate • B) Choline and acetyl-CoA • C) ATP and glutamate • D) Calcium and choline 16. The enzyme that synthesizes ACh is: • A) Acetylcholinesterase • B) Monoamine oxidase • C) Choline acetyltransferase (ChAT) • D) Tyrosine hydroxylase 21. Bungarotoxin, found in snake venom, causes: • A) Spastic muscle contractions • B) Irreversible inhibition of ACh receptors • C) Pain relief • D) Increased muscle tone Neuromuscular Stimulants 22. Drugs like neostigmine enhance NMJ activity by: • A) Blocking ACh receptors • B) Stimulating ACh synthesis • C) Inhibiting acetylcholinesterase • D) Opening calcium channels 23. Continuous muscle contraction due to excess ACh is called: • A) Flaccid paralysis • B) Tetany • C) Synaptic fatigue • D) Hyperreflexia Clinical Application 25. Myasthenia gravis is caused by: • A) Excess ACh • B) Genetic mutation in troponin • C) Autoantibodies against nicotinic receptors • D) Increased calcium influx 26. The most effective treatment for myasthenia gravis is: • A) Beta-blockers • B) Anticholinesterase drugs • C) Calcium supplements • D) Botulinum toxin 27. Eaton-Lambert syndrome involves: • A) Muscle fiber degeneration • B) Impaired release of ACh due to presynaptic calcium channel defect • C) Inhibition of AChE • D) GABA deficiency General 28. ACh binds to which receptor type at the NMJ? • A) Muscarinic • B) Nicotinic • C) Adrenergic • D) Dopaminergic 29. ACh is mainly degraded in: • A) Liver • B) Kidney • C) Synaptic cleft • D) Bloodstream