Describe the ionic and other events leading up to the release of

neurotransmitter at the vertebrate neuromuscular junction. What

events occur in the presynaptic cell consequent upon the release of
neurotransmitter?

The neuromuscular junction (NMJ) is the synapse or junction of the axon terminal of
a motor neuron with the motor end plate. The motor end plate is the highly-excitable
region of muscle fiber plasma membrane responsible for initiation of action potentials
across the muscle's surface, ultimately causing the muscle to contract. In vertebrates,
the signal passes through the neuromuscular junction via the neurotransmitter
acetylcholine.

The neuromuscular junction is the location where the neuron activates muscle
to contract, by releasing neurotransmitter. Before the neurotransmitter is released, an
action potential must arrive a the presynaptic neuron terminal. This causes the
voltage-dependent calcium channels to open and for calcium ions to flow from the
extracellular fluid into the presynaptic neuron's cytosol.

This influx of calcium ions causes vesicles, which contain the noted
neurotransmitter, to ‘fuse’ to the presynaptic neuron's cell membrane, resulting in the
neurotransmitter leaving the vesicle and entering the synapse of the cell. This process
is known as exocytosis. The neurotransmitter, acetylcholine, once it has diffused into
the synapse, binds to the nicotinic acetylcholine receptors, which are found in the
motor end plate. These receptors are ligand-gated ion channels, and once
acetylcholine has binded to the receptors, it causes the channels to open. Once
opened, sodium ions are able to flow in and potassium ions are able to flow out of the
muscle's cytosol. However, due to the differences in electrochemical gradients across
a plasma membrane, more sodium ions move in than potassium ions move out. This
produces a ‘local depolarisation’ of the motor end plate, which is known as an end-
plate potential (EPP).

It is this act of depolarisation that causes the spread across the surface of the
muscle fiber of depolarisation. This causes the excitation/ contraction of the NMJ,
causing the muscle to contract. The action of acetylcholine ends when an enzyme,
(acetylcholinesterase), degrades part of the neurotransmitter (producing choline and
an acetate group) and the rest of it diffuses away. The choline produced by the action
of this enzyme is recycled, as it is transported, through reuptake, back into the
presynaptic terminal, where it is used to synthesise new acetylcholine molecules.

These chains of events can be referred to as the excitation-contraction coupling of a

skeletal muscle.