neuromuscular junction

DR NILESH KATE

MBBS,MD ASSOCIATE PROF

DEPT. OF PHYSIOLOGY

NEURO-MUSCULAR JUNCTION.

OBJECTIVES. To draw the schematic diagram of Neuro-muscular

junction. To describe the events of Neuromuscular

transmission Classify neuromuscular blockers & give mechanism

of action Name common disorders of neuromuscular junction. Applied Aspects .

Wednesday, May 3, 2023

INTRODUCTION Neuro-muscular

junction/ Myoneural junction/Motor end plate.

Junction between Motor neuron & Muscle fibre.

Action potential from nerve is transmitted to muscle through this junction.


STRUCTURE Terminal button Presynaptic

membrane Synaptic cleft Postsynaptic

membrane


PRESYNAPTIC PORTION AXON TERMINAL

Neuron innervating skeletal muscle fibre – Motor Neurons

Near muscle fibre it looses its myelin sheath & divides into axon terminals

Each terminal is expanded at its tip to form Synaptic Knob ( Terminal Button)


PRESYNAPTIC PORTION AXON TERMINAL

The motor neuron its axon, its terminal with muscle fibre it supplies – form MOTOR UNIT.

Terminal button lies in a groove- Synaptic Trough.

Vesicles gather at specific points – Active Zones – Membrane at active zone modified to form Dense Bars – contains numerous voltage gated Ca channels.


SYNAPTIC CLEFT 50-100 nm wide. Filled with extracellular fluid Muscle fibre is covered by

basement membrane or basal lamina.

It contains AchE (acetyl-choline-esterase)

It hydrolyses Ach into Acetate & Choline.


POST SYNAPTIC MEMBRANE (END PLATE MEMBRANE)

It’s a part of sarcolemma & lies under terminal button.

It is thrown into several folds – Junctional Folds so increases end plate membrane surface area.

Contains Ach-receptors which contains voltage gated Na channels


ACETYL CHOLINE RECEPTORS Nicotinic type 15-40 millions/end plate. Chemically gated ion

channels Blocked by a-

Bungarotoxin. Contains voltage gated Na

channels & allow passage of only Cations.


NEUROMUSCULAR TRANSMISSION

Def – Transmission of impulses from motor neuron to skeletal muscle fibre.

Mechanism 3 parts Presynaptic events Synaptic events Post synaptic events.


PRE-SYNAPTIC EVENTS Main Purpose – To release acetyl choline into

synaptic cleft. Steps –

Action potential arrive at axon terminal & Depolarize membrane of terminal button.

Activate & open voltage gated Ca channels-Ca influx – increases movements of Microtubules & Microfilamants- causes migration of Neurotransmitter vesicles to pre-synaptic membrane - DOCKING

Release acetylcholine into cleft by Exocytosis.


PRE-SYNAPTIC EVENTS Quantal Release

One vesicle of acetyl choline – Quanta

Process of release of 1 vesicle is Quantal Release

Sir Katz, Euler & Axelrod received Nobel prize in 1970 for Quantal release phenomenon


SYNAPTIC CLEFT EVENTS Main Purpose –

Binding of acetylcholine to receptors at post synaptic membrane.

On the way some are hydrolyzed by AchE & remaining act on receptors.


POST SYNAPTIC EVENTS.

MAIN PURPOSE – Generate Action Potential in sarcolemma.

Acetylcholine diffuses into cleft & bind with post-synaptic acetylcholine receptors.

Receptors are Acetylcholine Gated Ion Channels.

Ion channels has 5 sub uints When 2 molecules are attached conformational

change occurs in tubular channels & open it & increases Na influx.


DEVELOPMENT OF ENDPLATE POTENTIAL

RMP of postsynaptic membrane is -80 to -90 mV. Influx of Na channels causes local positive potential

change – END PLATE POTENTIAL. It’s localized, Non-Propogated, Does not obey All

or None Law. But when critical level of -60mv reached triggers

action potential in muscle fibre in both direction.


MINIATURE ENDPLATE POTENTIAL

At rest, small quantity of acetyl choline are released from nerve terminal.

Each vesicle release produces weak end plate potential about 0.5mv – Miniature End Plate Potential.


REMOVAL OF ACETYLCHOLINE BY CHOLINESTERASE

Within 1 ms by 2 ways Mostly destroyed by

Acetylcholinestarase in synaptic cleft.

Remaining Diffuses Out of synaptic space & no longer available for action.



INITIATION OF THE ACTION POTENTIAL IN MUSCLE FIBRE.

DRUGS AFFECTING NEUROMUSCULAR JUNCTION.

Neuromuscular Blockers – this block neuromuscular transmission at junction. Curare Bungarotoxin Succinylcholine and

carbamylcholine Botulinum toxin


NEUROMUSCULAR BLOCKERS Curare – active

principle D-Tubocurarine (Cobra)

Block by combine with Ach-receptors.

So Ach cannot act on receptors & No End Plate Potential develop

So these are receptor blockers.


NEUROMUSCULAR BLOCKERS Bungarotoxin –

Venom of deadly snake. Krait. Also block N-M junction

by combining with acetylcholine receptors.


NEUROMUSCULAR BLOCKERS Succinylcholine &

Carbamylcholine – act like acetyl choline & Depolarizes post synaptic membrane

But these are not destroyed by cholinesterase – so muscle remain in depolarized state for a long time.

So these block Myoneural junction by keeping the muscle in depolarized state.


NEUROMUSCULAR BLOCKERS Botulinum Toxin –

derived from bacteria Clostridium Botulinum.

Block the junction by preventing the Release Of Acetyl Choline from terminal button.


NEUROMUSCULAR STIMULATORS

Drugs having acetylcholine like action-

Methacholine, Carbachol & Nicotin

But these are either not destroyed or destroyed very

slowly by acetylcholinesterase so causes repeated

stimulation & continuous action of muscle – Muscle

spasm.


NEUROMUSCULAR STIMULATORS

Drugs that Inactivate the enzyme Cholinesterase

(Anticholinesterase) – Neostigmine,

Physostigmine & Disopropylflurophosphate

(DFP)

So it leads to repeated stimulation & continuous action of

muscle. E.g – Laryngeal Spasm.


DISORDERS OF NEUROMUSCULAR JUNCTION.

Myasthenia Gravis Auto Immune disease. Anti bodies are

produced against Acetylcholine Receptors & destroy these channels



So acetyl choline released will not produce adequate end plate potential & excite muscle fibre

So patient dies of paralysis of Respiratory Muscles.



Lambert-Eaton syndrome.

Anti bodies are produced against calcium channels present on pre-synaptic membrane – so Ca influx decrease & decreases release of acetyl choline


Thank You

neuromuscular junction

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