End-plate potential
When an action potential reaches the axon terminal of a motor neuron, vesicles carrying neurotransmitters (mostly acetylcholine) are exocytosed and the contents are released into the neuromuscular junction.
In the absence of an action potential, acetylcholine vesicles spontaneously leak into the neuromuscular junction and cause very small depolarizations in the postsynaptic membrane.
In order for a muscle to contract, an action potential is first propagated down a nerve until it reaches the axon terminal of the motor neuron.
The motor neuron then innervates the muscle fibers to contraction by causing an action potential on the postsynaptic membrane of the neuromuscular junction.
During fetal development acetylcholine receptors are concentrated on the postsynaptic membrane and the entire surface of the nerve terminal in the growing embryo is covered even before a signal is fired.
Five subunits consisting of four different proteins from four different genes comprise the nicotinic acetylcholine receptors therefore their packaging and assembly is a very complicated process with many different factors.
Vesicle depletion from the readily releasable pool occurs during high frequency stimulation of long duration and the size of the evoked EPP reduces.
In 1970, Bernard Katz from the University of London won the Nobel Prize for Physiology or Medicine for statistically determining the quantal size of acetylcholine vesicles based on noise analysis in the neuromuscular junction.
The vesicles release their entire quantity of acetylcholine and this causes miniature end plate potentials (MEPPs) to occur which are less than 1mV in amplitude and not enough to reach threshold.
[7] Miniature end plate potentials are the small (~0.4mV) depolarizations of the postsynaptic terminal caused by the release of a single vesicle into the synaptic cleft.
[8] During experimentation with MEPPs, it was noticed that often spontaneous action potentials would occur, called end plate spikes in normal striated muscle without any stimulus.
Recent experiments have shown that these end plate spikes are actually caused by muscle spindles and have two distinct patterns: small and large.
This allows for increased flow of sodium and potassium ions, causing depolarization of the sarcolemma (muscle cell membrane).
The small depolarization associated with the release of acetylcholine from an individual synaptic vesicle is called a miniature end-plate potential (MEPP), and has a magnitude of about +0.4mV.
This depolarization voltage spike triggers an action potential which propagates down the postsynaptic membrane leading to muscle contraction.
In a normal muscular contraction, approximately 100-200 acetylcholine vesicles are released causing a depolarization that is 100 times greater in magnitude than a MEPP.
Several diseases and problems can be caused by the inability of enzymes to clear away the neurotransmitters from the synaptic cleft leading to continued action potential propagation.
[11] Myasthenia gravis is an autoimmune disease, where the body produces antibodies targeted against the acetylcholine receptor on the postsynaptic membrane in the neuromuscular junction.
It was found that a combination of the jitter and blocking rate of the acetylcholine receptors caused a reduced end-plate potential similar to what is seen in cases of myasthenia gravis.
[12] Research of motor unit potentials (MUPs) has led to possible clinical applications in the evaluation of the progression of pathological diseases to myogenic or neurogenic origins by measuring the irregularity constant related.
[13] Lambert–Eaton myasthenic syndrome is a disorder where presynaptic calcium channels are subjected to autoimmune destruction which causes fewer neurotransmitter vesicles to be exocytosed.
Alpha-latrotoxin found in black widow spiders causes a massive influx of calcium at the axon terminal and leads to an overflow of neurotransmitter release.
