Neuromuscular Junction

NEUROMUSCULAR JUNCTION

Dr. Niranjan Murthy H L Asst. Prof., Dept. of Physiology Sree Siddhartha Medical College & Hospital, Tumkur

NEUROMUSCULAR JUNCTION PHYSIOLOGIC ANATOMY MECHANISM OF NEUROTRANSMITTER RELEASE SIGNAL TRANSDUCTION AT POST-SYNAPTIC MEMBRANE ELECTRICAL EVENTS AT MOTOR ENDPLATE DRUGS ACTING ON NMJ MYASTHENIA GRAVIS AND LAMBERT- EATON SYNDROME NMJ IN CARDIAC AND SMOOTH MUSCLES

NEUROMUSCULAR JUNCTION- STRUCTURE

STRUCTURE OF NMJ • Alpha Motor neuron- myelinated • End feet or terminal buttons- loses myelin sheath • Synaptic cleft- 50 to 100nm wide • Post-synaptic gutter • Sub-synaptic clefts- increases surface area • Acetylcholine receptors- 15 to 40 million • MOTOR END-PLATE

SYNTHESIS AND STORAGE OF Ach • Choline+Acetyl Co-A+ATP Choline acyltransferase

Acetyl-choline cholinesterase

Choline + Acetate

RELEASE OF Ach • Action potential at end-feet • Opening of voltage-gated Ca2+ channels • Exocytosis of Ach- 60 vesicles with 10,000 molecules each are released

SIGNAL TRANSDUCTION •Ach-gated ion channels has 5 subunits: 2α,1β,1γ and 1ε •2 Ach molecules binds to 2α subunits •Opening of the channel to cations •Influx of Na+ ions •End-plate potential

ELECTRICAL EVENTS • RMP of muscle membrane is –90mv • Na+ influx raises the end-plate potential (EPP) by 50-75mv • Opening of voltage-gated Na+ channels • Propogated action potential • MINIATURE END-PLATE POTENTIAL

DRUGS ACTING ON NMJ • DRUGS THAT INCREASE ACTIVITY OF NMJ • Drugs with Ach-like action Eg: Nicotine, Methacholine & Carbachol • Drugs that inactivate acetylcholinesterases Eg: Physostigmine, Neostigmine, Diisopropyl fluorophosphate

• DRUGS THAT BLOCK NMJ A) By inhibiting Ach release Eg: Botulinum toxin B) By antagonizing Ach action 1. By competitive inhibition Eg: Curariform drugs 2. By persistent depolarisation Eg: Succinylcholine

MYASTHENIA GRAVIS

MYASTHENIA GRAVIS • • • •

auto-immune disorder Antibodies against Ach-gated channels Causes endocytosis of receptors C/f: muscle weakness, ptosis, respiratory failure • Rx- Anticholinesterases like neostigmine, physostigmine

LAMBERT-EATON SYNDROME • Antibodies against Voltage-gated Ca2+ channels at end-feet • Reduced Ach release • Muscle strength increases with prolonged contractions

NMJ IN SMOOTH AND CARDIAC MUSCLES • Cholinergic as well as noradrenergic fibers • Varicosities- enlargements devoid of schwann cells and containing vesicles • Noradrenergic neurons have upto 20,000 varicosities per neuron each 5μm apart • One neuron innervate many effector cells • Diffuse junctions and contact junctions • Synapse en passant • Neurotransmitters- Ach, Noradrenaline,etc • Excitatory or inhibitory junctional potentialsdepends on the type of receptor

NEUROMUSCULAR JUNCTION