The synapse and the end plate are separated by a distance of 20nm and is
filled with extra cellular fluid.
There is a transmission of action potential in the motor
neuron which triggers release of calcium by opening of calcium voltage
gated channels. Calcium enters extracellular fluid into intracellular fluid and
triggers release of acetylcholine by exocytosis of vesicles present in the
Acetylcholine is secreted by the pre synaptic nerve terminal.
Ach binds to receptors on the post synaptic membrane on the end plate
where the Na Ligand gates open, thus enabling Na (sodium) to enter the extracellular
fluid from intracellular fluid entry of sodium.
In th non-contracting state, the charge inside of the cell is negative
and outside is positive, which is known as ”polarised
When sodium ligand voltage gates are opened, the sodium floods into the
cell and potassium comes out of the cell, which results in building up of
positive charge in the inside of cell and positive on the outside of the cell
also- this is known as ”depolarised state”.
When a threshold potential is reached, there is ”all or none” response and
there is firing of action potential throughout the sarcolemma of the skeletal
The electrical change from -70mV to +30mV opens up other ligand gates,
the electric current is spread across sarcolemma. This electric current or the
action potential travels from plasma membrane into the ‘T tubules’.
From T-tubules the current travels to the sarcoplasm which opens the ligand
gates present in sarcoplasm reticulum, causing more calcium to be released
which is needed to contract the muscle.
Botulinum toxin comes from anaerobe
gram positive bacilli known as ‘Clostridium Botulinum’ and is a neuro toxin,
causes flaccid paralysis of muscle.
The neurotoxin has 8 types immunologically: A, B, C (1,2), D, E, F, G. The
toxins are synthesized during cell growth and released by cell lysis.
It contains a heavy chain and
a light chain. The toxin enters as
the body as vesicle via endocytosis.
Membrane of axon terminal has ganglioside (lipid molecule) known as GT
1b, to which the botulinum toxin binds with the heavy chain and a process known
as Clathrin mediated endocytosis
happens, engulfing the toxin in in the form of a vesicle. This vesicle contains
heavy and light chain when in the cytoplasm and are known as endosomes.
There are changes in the pH
changes inside the endosome due to which, there is a separation of heavy and
light chain, with light chain entering the cytoplasm.
These light chains in cytoplasm will cleave the snare proteins:
(SNAP 25, Syntaxin 1, Synaptobrevin 2).
The cleavage sites for botulinum toxin A, B, C, D, E are different and
that is the reason for different durations of muscle relaxation
The toxin inhibits exocytosis
Proteins known as ‘snares SNAP (Soluble NSF Attachment
Protein) Receptor mediate docking of
vesicles with presynaptic membranes of neurons.
There are 2 types of snares:
1. T Snares (target snares): snap-25 and syntaxin 1
2. V- Snares (vesicles snares): Synaptobredin
In the plasma membrane there are multiple formations of core snare complex
made by the Syntaxin 1, SNAP 25 and
synaptobredin 2, intertwined with each other so that they bundle together and
known as ”core snare complex’..
Clamp theory: In the neurons- a
protein known as ”Complexin” is present in between the plasma membrane and
the vesicle which help in docking the vesicles to the membrane, ready to release
the neurotransmitter into the synaptic cleft. Presence of complexin inhibits
fusion of vesicle to cell membrane
Due to action potential, when intraneuronal calcium is released, it binds
to a specific protein- Synaptotagmin,
in neurons which removes or inactivates Complexin triggering the
complete fusion of the vesicle with the target membrane and there is release of
transmitter by exocytosis.