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Neuromuscular Junction (NMJ)

Synaptic contact between somatic motor nerve and a skeletal muscle fiber

Transfer of impulse from nerve to muscle

Events at nerve terminal

►Arrival of action potential

►Opening of voltage gated Ca++channels

►Ca++influx in nerve terminal

►Docking of ACh vesicles

►Release of ACh into synaptic cleft

►Events at muscle fiber membrane

►Binding of Ach to nicotinic receptors

►2 molecules bind with 2 αsubunit of receptor

►Opening of Ach gated cation channels

►Influx of Na+, Ca++(efflux of K+also occurs)

►Generation of end plate potential (EPP)

Neuromuscular junction

End plate potential

►Graded potential generated in muscle fiber due to influx of Na+through ACh gated cation channels

►Brings the voltage to threshold for action potential

►Normally three times greater than threshold (↑↑↑ safety factor)

End plate potential

►If less than threshold

►Action potential in muscle fiber will not be generated

►Generation of action potential in muscle fiber

►Rise in voltage to threshold due to EPP

►Opening of voltage gated Na+channels

►Generation of action potential

►Spread of action potential along sarcolemma and into ‘T’ tubules

Removal of Ach from synaptic cleft

►Diffusion into the adjacent area

►Acetylcholinesterase

►Enzyme present in synaptic cleft

►Breaks Ach into choline and acetate (within 1 ms)

►Choline is reuptaken into nerve terminal and reused to form ACh

►Miniature end plate potential

►Weak EPP due to spontaneous release of Ach

►Up to 0.5 mv

►Can not produce action potential

Chemicals affecting NMJ

NMJ stimulants

►Acetylcholine like drugs

►Nicotine, methacholine, carbachol

►Stimulate Ach receptors

►Anticholinesterases (used as drugs)

►Neostigmine, physostigmine, edrophonium (tensilon)

►Temporarilyinhibit AChE

►NMJ stimulants

►Anticholinesterases -inhibit AChE irreversibly or for prolonged period

►Organophosphates

►irreversibly inhibit AChE

►Diisopropyl fluorophosphate (nerve gas)

►Inhibits AChE for weeks

NMJ blockers

►Curare -arrow head poison

►Blocks ACh receptors

►Cant be destroyed by AChE

►Death occurs due to paralysis of respiratory muscles (asphyxiation)

►Curariform durgs (gallamine)

►Used for muscle relaxation during surgery

NMJ blockers

►Botulinum toxin

►Causes food poisoning -botulism

►Blocks release of ACh

►Death may occur due to asphyxiation

►Therapeutic use of botulinum (botox)

►Cosmetic -to treat wrinkles

►Chronic back pain etc

Myasthenia gravis

►A neuromuscular disorder leading to muscular weakness & fatigability

►Etiology

►Autoimmunity -antibodies against ACh receptors

►Destruction of receptors

►Blockage of receptors

Pathophysiology

►Nicotinic receptors available for ACh are too less

►EPP less than threshold (Safety factor < 1)

►No action potential in muscle fiber

►No muscular contraction

Clinical features

►Easily fatigability and muscular weakness

►Diplopia, ptosis

►Disphagia

►Disarthria

►Paralysis of respiratory muscles and death

Incidence

►1 in 20000

►More common in women

►Death may occur due to paralysis of respiratory muscles

Treatment

►Anticholinesterases

►Neostigmine, physostigmine etc

►Immunosuppresion

►Plasmapheresis

►Thymectomy

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2 comments

  1. Jeez, it’s unusual to find such a great posting

  2. Wow that was really interesting, altought i would add few more deeper thoughts

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