The end plate potential (EPP) is a specialized electrical signal that links the nervous system and skeletal muscle, initiating voluntary movement. It is a rapid, localized change in the electrical voltage across the muscle fiber membrane where it meets a motor nerve. This depolarization is the first step in transmitting the command from a motor neuron to the muscle cell, leading to muscle contraction.
The Neuromuscular Junction: Setting the Scene
The EPP occurs exclusively within a highly specialized structure called the neuromuscular junction (NMJ), which functions as a chemical synapse between a motor neuron and a muscle fiber. This junction is composed of three distinct but closely associated parts. The presynaptic terminal is the bulbous end of the motor neuron’s axon, containing thousands of tiny vesicles filled with the neurotransmitter acetylcholine (ACh).
Separating these two structures is the narrow synaptic cleft, only about 30 to 50 nanometers wide. The motor end plate is highly folded, creating junctional folds that significantly increase the surface area available to receive the signal. These folds are densely packed with nicotinic acetylcholine receptors (nAChRs), which are the targets for the neurotransmitter.
Generating the End Plate Potential
The generation of the EPP begins when an electrical impulse, or action potential, arrives at the presynaptic terminal of the motor neuron. This electrical signal triggers the opening of voltage-gated calcium ion (\(\text{Ca}^{2+}\)) channels in the terminal membrane, allowing an influx of \(\text{Ca}^{2+}\) ions from the outside environment. The sudden increase in internal calcium concentration acts as a signal, prompting synaptic vesicles to fuse with the presynaptic membrane and release their contents into the synaptic cleft.
This release mechanism is quantal, meaning that ACh is released in fixed packets, with each packet originating from a single vesicle containing thousands of ACh molecules. The released ACh rapidly diffuses across the narrow synaptic cleft and binds to the nicotinic receptors on the motor end plate. The binding of two ACh molecules to a receptor causes the receptor’s ion channel to open briefly, allowing positively charged ions to flow across the muscle membrane.
The open channel is permeable to both sodium (\(\text{Na}^+\)) and potassium (\(\text{K}^+\)) ions. However, the electrochemical driving force for \(\text{Na}^+\) to enter the cell is much stronger than the force for \(\text{K}^+\) to leave, resulting in a net influx of positive charge. This rapid, transient depolarization of the motor end plate membrane is the EPP, and its amplitude relates directly to the amount of ACh released and the number of receptors activated.
EPP Versus the Muscle Action Potential
The end plate potential is fundamentally different from the muscle action potential it is designed to trigger. The EPP is categorized as a graded potential, meaning its strength varies in proportion to the amount of ACh released. It is a localized response that passively spreads only a short distance along the muscle fiber membrane before dissipating. The EPP typically has an amplitude of about 10 to 20 millivolts but does not propagate itself.
In contrast, the muscle action potential is an all-or-nothing electrical event that is self-propagating along the entire length of the muscle fiber. The role of the EPP is to depolarize the muscle fiber membrane until it reaches a specific threshold voltage. Once this threshold is attained, it activates nearby voltage-gated sodium channels, initiating the full-scale, non-decremental action potential that travels away from the end plate.
The neuromuscular junction is designed with a high degree of transmission reliability, often referred to as a high “safety factor.” This factor measures how much the EPP exceeds the threshold needed to initiate a muscle action potential. A high safety factor ensures that a single nerve impulse reliably triggers the muscle action potential, preventing voluntary muscle movements from failing due to minor fluctuations.
Factors Influencing EPP Strength
The amplitude of the EPP can be altered by various physiological, pharmacological, and pathological factors. Anything that decreases the amount of acetylcholine released from the nerve terminal will reduce the EPP amplitude. For example, botulinum toxin cleaves proteins required for vesicular fusion, severely inhibiting ACh release and leading to a low-amplitude EPP and muscle paralysis.
Conversely, conditions that affect the postsynaptic side, the motor end plate, also influence the EPP strength. The autoimmune disease Myasthenia Gravis causes the body to produce antibodies that attack and destroy the nicotinic acetylcholine receptors. This reduction in the number of functional receptors means that even a normal release of ACh results in a much smaller EPP, which may fail to reach the threshold necessary to trigger a muscle action potential. The resulting low EPP causes the muscle weakness and fatigability characteristic of the disease.
Some drugs can temporarily increase EPP strength by inhibiting acetylcholinesterase, the enzyme that normally breaks down ACh in the synaptic cleft. By slowing the breakdown, these drugs allow ACh to remain bound to the receptors longer, increasing the EPP’s duration and amplitude. This principle is utilized in the treatment of Myasthenia Gravis, where inhibitors help maximize the effect of the remaining functional receptors.