lecture on the physiology of neuromuscular junction (nmj) by dr. roomi

8/13/2019 Lecture on the Physiology of Neuromuscular Junction (NMJ) by Dr. Roomi

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NEURO-MUSCULAR JUNCTION

By

Dr. Mudassar Ali Roomi (MBBS, M. Phil)



NEUROMUSCULAR JUNCTION (NMJ)

• Motor nerve fibers whichsupply the muscle losetheir myelin sheath nearmuscle fiber.

• Then terminal part dividesinto motor nerve terminals /end feet / synaptic knobs.

• Each end foot forms neuro-muscular junction with amuscle fiber at its mid-point.

•NMJ is a chemical synapse.**




• At NMJ, muscle fiber iscalled motor end plate.Here is an invaginationcalled as synaptic gutter.

• End foot fits into thegutter to form NMJ,but no continuitybetween nerve & muscle.

• Membrane of motor endplate is thrown into folds sub-neural cleft.



NEUROMUSCULAR

JUNCTION (NMJ)

• End foot has:Mitochondria & pre-synaptic vesicles withneurotransmitter:Acetylcholine.

• Vesicles are synthesized incell body & thentransported to nerveterminal & mitochondriaprovide energy for it.

• In basal lamina isAcetylcholine esterase enzyme is present.



Mechanism of neuro-muscular

transmission:



Mechanism of neuro-muscular transmission:

• Nerve impulse reaches the nerve terminal opening of voltagegated calcium channels.

• Calcium (from ECF) enters nerve terminal agitation of some of

the synaptic vesicles (125 -150 vesicles become agitated & fuse withmembrane) release their acetylcholine into synaptic cleft byexocytosis.

• Ach (released) binds with receptors at motor end plate

opening of Ach gated channels

sodium influx

end platepotential (EPP) (which is localized potential change).



End plate potential (EPP)

• 50-70 mV is amplitude of EPP.

• Because of EPP Threshold for action potential isreached (-65 mV).

• If RMP is -90 mV, then threshold is -65 mV, we need 25mV potential change.

• Purpose of EPP is to reach the threshold of action

potential.

• So voltage of EPP is much more than required, becauserequired is only 25 mV. It is called as SAFETY FACTOR.



End plate potential (EPP) Action potential

1. Proportional to stimulus strength

(graded)

Independent of stimulus strength

(all or none)

2. Not propagated but decremental

with distance

Propagated, unchanged in magnitude

3. Exhibits summation Summation not possible

4. magnitude: low Magnitude: high

5. Refractory period: absent Refractory period: present

6. duration: Longer duration: shorter



How the action of

Acetylcholine is finished??

• Ach once released,remains bound withreceptors only for 1 msec.

• Some diffuses out to ECF& rest is hydrolyzed byenzyme acetylcholineesterase.

• Ach (on hydrolysis) Choline + Acetate



MYASTHENIA GRAVIS:

• A rare auto-immune disease.• More common in females

• Voltage of EPP is very low (Miniature EPP) action

potential is not followed. At rest normally, a fewsynaptic vesicles liberate Ach small change in EPP(about 0.5 mV) called MEPP.

• Impulse fails to transmit through NMJ Severe

muscle weakness & fatigue.

• Auto-antibodies are produced against Ach gatedreceptors & these receptors are destroyed irreversibly.



Clinical features of Myasthenia Gravis

• weakness of Extra-

ocular muscles ptosis

(drooping of upper

eyelids),• diplopia (double vision)

• difficulty in Swallowing,

•

weakness of Respiratoryand Facial muscles



TREATMENT of Myasthenia Gravis

1. Anti-cholinesterase drugs (neostigmine,Physostigmine) markedimprovement.

– Mechanism of action:anticholine esterases inhibitenzyme choline esterase Ach not hydrolyzed moreAch available for availablenumber of receptors.

2. Plasmapharesis: it maysometimes be needed toremove the autoantibodiesfrom the serum.

3. Glucocorticoids (steroids)may also be required toinhibit the immunity.



Evidence that Myasthenia Gravis is an autoimmunedisease:

1. Auto antibodies detected in patient’s blood.

2. In many of these cases, thymus is enlarged &thymectomy is of benefit.



DESCRIPTION OF a typical CASE of Myasthenia

Gravis

• An 18-year-old college woman comes to the studenthealth service complaining of progressive weakness.She reports that occasionally her eyelids "droop" andthat she tires easily, even when completing ordinary

daily tasks such as brushing her hair. She has fallenseveral times while climbing a flight of stairs. Thesesymptoms improve with rest. The physician ordersblood studies, which reveal elevated levels ofantibodies to ACh receptors. Nerve stimulation studies

show decreased responsiveness of skeletal muscle uponrepeated stimulation of motor neurons. The woman isdiagnosed with myasthenia gravis and is treated withthe drug neostigmine. After treatment, she reports areturn of muscle strength.



EXPLANATION OF CASE

• This young woman has classic myasthenia gravis. In theautoimmune form of the disease, antibodies are producedto ACh receptors on the motor end plates of skeletalmuscle.

• Her symptoms of severe muscle weakness (eye muscles;arms and legs) are explainable by the presence ofantibodies that block ACh receptors. Although ACh isreleased in normal amounts from the terminals ofmotoneurons, binding of ACh to its receptors on the motorend plates is impaired. Because ACh cannot bind,

depolarization of the motor end plate (end plate potential,EPP) will not occur, and normal action potentials cannot begenerated in the skeletal muscle. Muscle weakness andfatigability ensue.

lecture on the physiology of neuromuscular junction (nmj) by dr. roomi

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