Myasthenia Gravis - Anatomy & Physiology

By: Dr. Swathi

Prof Dr A.Gowrishankar’s unit

Each muscle fibre is connected to a nerve fibre branch coming from a motor neuron

Stimulation from motor neurons initiates the contraction process.

The motor neuron and all the muscle fibres it innervates are called a motor unit.

The site at which motor neuron attaches on the muscle cell is known as the neuromuscular junction

Details of these junctions vary in different skeletal muscle fibres as follows:

1) Motor end plates

2) En grappe endings intrafusal

fibres

3) Trail endings

Sole plate( it’s a specialized area of the muscle fibre) + axon terminal motor end plate

MOTOR END PLATE COMPRISES OF:

Pre synaptic membrane(axolemma) Synaptic cleft primary cleft (40nm) secondary(subneural) cleft Post synaptic membrane

SARCOLEMMA

Axon terminals contain synaptic vesicles & are rich in mitochondria

Pre synaptic terminal contains voltage gated Ca2+ channels

In the region of the sole plate sarcoplasm is rich in mitochondria, ER & golgi complexes

Post synaptic membrane contains Ach receptors & voltage gated Na2+ channels

An AP propagates down the axon

invades and depolarizes the presynaptic

terminal region

Ca2+ flows into the boutons through voltage-activated Ca2+ channels

Fusion of synaptic vesicles with pre-synaptic membrane & the release of "packets" or quanta of transmitter into the cleft.

In the case of the neuromuscular junction, the transmitter released is acetylcholine(ACh).

It is important to note that the amount of transmitter released is directly related to the amount of Ca2+ that enters the bouton, which is directly related to the number, amplitude and duration of the invading action potentials.

The Ca2+ channels involved are not located along the axon, only at the terminal ‘boutons’.

The vesicles fuse to the terminal membrane via specialized docking proteins.

Vesicle membrane is recycled, but that system can be overwhelmed

ACh diffuses across the cleft. This takes time (up to several hundred microsec).

ACh binds to Nicotinic ACh receptors in the post-synaptic membrane, opening monovalent cation channels

Channel opening depolarizes the post-synaptic membrane, creating an endplate potential (EPP).

If EPPs exceeds a threshold value

Voltage-activated Na+ channels open giving rise to a muscle AP.

Termination of the transmission process occurs via hydrolysis of ACh by acetylcholinesterase present in the junction.

Three possible immunological mechanisms—

1)Actual degradation the receptor site by complement activation by IgG

2)Accelerating the degradation of anticholinesterase receptor through the cross-linking phenomenon.

3)Directly blocking the receptor site.

The no of AChRs at the neuromuscular junction are reduced to approx 20% of normal levels

EPP is reduced in amplitude & fails to reach the threshold

EPP becomes smaller during repeated efforts

THANK

U