End-plate potential - AbsoluteAstronomy.com

End plate potentials (sometimes called "end plate spikes") are the depolarizations of skeletal muscle

Skeletal muscle

Skeletal muscle is a form of striated muscle tissue existing under control of the somatic nervous system- i.e. it is voluntarily controlled. It is one of three major muscle types, the others being cardiac and smooth muscle...

fibers caused by neurotransmitters binding to the postsynaptic membrane in the neuromuscular junction

Neuromuscular junction

A neuromuscular junction is the synapse or junction of the axon terminal of a motor neuron with the motor end plate, 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...

. They are called "end plates" because the postsynaptic terminals of muscle fibers have a large, saucer-like appearance. When an action potential

Action potential

In physiology, an action potential is a short-lasting event in which the electrical membrane potential of a cell rapidly rises and falls, following a consistent trajectory. Action potentials occur in several types of animal cells, called excitable cells, which include neurons, muscle cells, and...

reaches the axon terminal

Axon terminal

Axon terminals are distal terminations of the branches of an axon. An axon nerve fiber is a long, slender projection of a nerve cell, or neuron, that conducts electrical impulses away from the neuron's cell body, or soma, in order to transmit those impulses to other neurons.Neurons are...

of a motor neuron

Motor neuron

In vertebrates, the term motor neuron classically applies to neurons located in the central nervous system that project their axons outside the CNS and directly or indirectly control muscles...

, vesicles carrying neurotransmitters (mostly acetylcholine

Acetylcholine

The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...

) are exocytosed

Exocytosis

Exocytosis , also known as 'The peni-cytosis', is the durable process by which a cell directs the contents of secretory vesicles out of the cell membrane...

and the contents are released into the neuromuscular junction. These neurotransmitters bind to receptors on the postsynaptic membrane and lead to its depolarization. In the absence of an action potential, acetylcholine vesicles spontaneously leak into the neuromuscular junction and cause very small depolarizations in the postsynaptic membrane. This small response (~0.5mV) is called a miniature end plate potential (MEPP) and is generated by one acetylcholine containing vesicle. It represents the smallest possible depolarization which can be induced in a muscle.

Neuromuscular junction

The neuromuscular junction is the synapse that is formed between an α motor neuron and the skeletal muscle fiber. When a muscle contracts, an action potential is 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.

Acetylcholine

End plate potentials are produced almost entirely by the neurotransmitter acetylcholine in skeletal muscle. Acetylcholine is the second most important excitatory neurotransmitter in the body following glutamate. It controls the somatosensory system

Somatosensory system

The somatosensory system is a diverse sensory system composed of the receptors and processing centres to produce the sensory modalities such as touch, temperature, proprioception , and nociception . The sensory receptors cover the skin and epithelia, skeletal muscles, bones and joints, internal...

which includes the senses of touch, vision, and hearing. It was the first neurotransmitter to be identified in 1914 by Henry Dale. Acetylcholine is synthesized in the cytoplasm of the neuron from choline

Choline

Choline is a water-soluble essential nutrient. It is usually grouped within the B-complex vitamins. Choline generally refers to the various quaternary ammonium salts containing the N,N,N-trimethylethanolammonium cation....

and acetyl-CoA

Acetyl-CoA

Acetyl coenzyme A or acetyl-CoA is an important molecule in metabolism, used in many biochemical reactions. Its main function is to convey the carbon atoms within the acetyl group to the citric acid cycle to be oxidized for energy production. In chemical structure, acetyl-CoA is the thioester...

. Choline acyltransferase is the enzyme that synthesizes acetylcholine and is often used as a marker in research relating to acetylcholine production. Neurons that utilize acetylcholine are called cholinergic neurons and they are very important in muscle contraction, memory, and learning.

Ion channels

The polarization of membranes is controlled by sodium

Sodium

Sodium is a chemical element with the symbol Na and atomic number 11. It is a soft, silvery-white, highly reactive metal and is a member of the alkali metals; its only stable isotope is 23Na. It is an abundant element that exists in numerous minerals, most commonly as sodium chloride...

, potassium

Potassium

Potassium is the chemical element with the symbol K and atomic number 19. Elemental potassium is a soft silvery-white alkali metal that oxidizes rapidly in air and is very reactive with water, generating sufficient heat to ignite the hydrogen emitted in the reaction.Potassium and sodium are...

, calcium

Calcium

Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...

, and chloride

Chlorine

Chlorine is the chemical element with atomic number 17 and symbol Cl. It is the second lightest halogen, found in the periodic table in group 17. The element forms diatomic molecules under standard conditions, called dichlorine...

ion channels. There are two types of ion channels involved in the neuromuscular junction and end plate potentials: voltage-gated ion channel

Voltage-gated ion channel

Voltage-gated ion channels are a class of transmembrane ion channels that are activated by changes in electrical potential difference near the channel; these types of ion channels are especially critical in neurons, but are common in many types of cells....

and ligand-gated ion channel

Ligand-gated ion channel

Ligand-gated ion channels are one type of ionotropic receptor or channel-linked receptor. They are a group of transmembrane ion channels that are opened or closed in response to the binding of a chemical messenger , such as a neurotransmitter.The binding site of endogenous ligands on LGICs...

. Voltage gated ion channels are responsive to changes in membrane voltage which cause the voltage gated ion channel to open and allows certain ions to pass through. Ligand gated ion channels are responsive to certain molecules such as neurotransmitters. The binding of a ligand

Ligand

In coordination chemistry, a ligand is an ion or molecule that binds to a central metal atom to form a coordination complex. The bonding between metal and ligand generally involves formal donation of one or more of the ligand's electron pairs. The nature of metal-ligand bonding can range from...

to the receptor on the ion channel protein causes a conformational change which allows the passing of certain ions.

Presynaptic membrane

Normally the resting membrane potential of a motor neuron is kept at -70mV to -50 with a higher concentration of sodium outside and a higher concentration of potassium inside. When an action potential propagates down a nerve and reaches the axon terminal of the motor neuron, the change in membrane voltage causes the calcium voltage gated ion channels to open allowing for an influx of calcium ions. These calcium ions cause the acetylcholine vesicles attached to the presynaptic membrane to release acetylcholine via exocytosis

Exocytosis

Exocytosis , also known as 'The peni-cytosis', is the durable process by which a cell directs the contents of secretory vesicles out of the cell membrane...

into the synaptic cleft.

Postsynaptic membrane

EPP are caused mostly by the binding of acetylcholine to receptors in the postsynaptic membrane. There are two different kinds of acetylcholine receptors: nicotinic and muscarinic. Nicotinic receptors are ligand gated ion channels for fast transmission. All acetylcholine receptors in the neuromuscular junction are nicotinic. Muscarinic receptors are G protein-coupled receptors that use a second messenger. These receptors are slow and therefore are unable to measure a miniature end plate potential (MEPP). They are located in the parasympathetic nervous system

Parasympathetic nervous system

The parasympathetic nervous system is one of the two main divisions of the autonomic nervous system . The ANS is responsible for regulation of internal organs and glands, which occurs unconsciously...

such as in the vagus nerve and the gastrointestinal tract

Gastrointestinal tract

The human gastrointestinal tract refers to the stomach and intestine, and sometimes to all the structures from the mouth to the anus. ....

.
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. The enzyme muscle-specific kinase (MuSK) initiates signaling processes in the developing postsynaptic muscle cell. It stabilizes the postsynaptic acetylcholine receptor clusters, facilitates the transcription of synaptic genes by muscle fiber nuclei, and triggers differentiation of the axon growth cone to form a differentiated nerve terminal. Substrate laminin induces advanced maturation of the acetylcholine receptor clusters on the surfaces of myotubes.

Synaptic Vesicles

All neurotransmitters are released into the synaptic cleft via exocytosis from synaptic vesicles. Two kinds of neurotransmitter vesicles exist: large dense core vesicles and small clear core vesicles. Large dense core vesicles contain neuropeptides and large neurotransmitters that are created in the cell body of the neuron and then transported via fast axonal transport down to the axon terminal. Small clear core vesicles transport small molecule neurotransmitters that are synthesized locally in the presynaptic terminals. Finalized neurotransmitter vesicles are bound to the presynaptic membrane. When an action potential propagates down the motor neuron axon and arrives at the axon terminal, it opens calcium channels and causes a depolarization of the axon terminal. This causes the release of the neurotransmitters via exocytosis. The vesicles are then recycled following a process known as the synaptic vesicle cycle. The retrieved vesicular membranes are passed through several intracellular compartments where they are modified to make new synaptic vesicles. They are then stored in a reserve pool until they are needed again for transport and release of neurotransmitters. Unlike the reserve pool, the readily releasable pool of synaptic vesicles is ready to be activated. Vesicle depletion from the readily releasable pool occurs during high frequency stimulation of long duration and the size of the evoked EPP reduces. This neuromuscular depression is due to less neurotransmitter release during stimulation. In order for depletion not to occur, there must be a balance between repletion and depletion which can happen at low stimulation frequencies of less than 30 Hz.
When a vesicle releases its neurotransmitters via exocytosis, it empties its entire contents into the synaptic cleft. Neurotransmitter release from vesicles is therefore stated to be quantal because only whole numbers of vesicles can be released. In 1970, Bernard Katz

Bernard Katz

Sir Bernard Katz, FRS was a German-born biophysicist, noted for his work on nerve biochemistry. He shared the Nobel Prize in physiology or medicine in 1970 with Julius Axelrod and Ulf von Euler...

from the University of London

University of London

-20th century:Shortly after 6 Burlington Gardens was vacated, the University went through a period of rapid expansion. Bedford College, Royal Holloway and the London School of Economics all joined in 1900, Regent's Park College, which had affiliated in 1841 became an official divinity school of the...

won the Nobel Prize

Nobel Prize

The Nobel Prizes are annual international awards bestowed by Scandinavian committees in recognition of cultural and scientific advances. The will of the Swedish chemist Alfred Nobel, the inventor of dynamite, established the prizes in 1895...

for Physiology or Medicine for statistically determining the quantal size of acetylcholine vesicles based on noise analysis in the neuromuscular junction. Using a book on mechanical statistics, he was able to infer the size of individual events going on at the same time.

The synaptic vesicles of acetylcholine are clear core synaptic vesicles with a diameter of 30 nm. Each acetylcholine vesicle contains approximately 5000 acetylcholine molecules. 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.

Miniature End Plate Potentials (MEPPs)

Miniature end plate potentials are the small (~0.5mV) depolarisations of the postsynaptic terminal caused by the release of a single vesicle into the synaptic cleft. Neurotransmitter vesicles containing acetylcholine collide spontaneously with the nerve terminal and release acetylcholine into the neuromuscular junction even without a signal from the axon. These small depolarizations are not enough to reach threshold and so an action potential in the postsynaptic membrane does not occur.
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. It was believed that these end plate spikes occurred as a result of injury or irritation of the muscles fibers due to the electrodes. Recent experiments have shown that these end plate spikes are actually caused by muscle spindles and have two distinct patterns: small and large. Small end plate spikes have a negative onset without signal propagation and large end plate spikes resemble motor unit potentials (MUPs). Muscle spindles are sensory receptors that measure muscle elongation or stretch and relay the information to the spinal cord or brain for the appropriate response.

Threshold potential (“All or nothing”)

When an action potential causes the release of many acetylcholine vesicles, each small depolarization (MEPP) sums together. This summation of MEPPs leads to a greater depolarization of the postsynaptic membrane and become an end plate potential. When the membrane reaches a certain value of depolarization (-65mV), the voltage gated ion channels in the postsynaptic membrane open causes in influx of sodium ions and a sharp spike in depolarization. This spike causes an action potential to occur and propagate down the postsynaptic membrane leading to muscle contraction.
In a normal muscular contraction, approximately 35 acetylcholine vesicles are released causing a depolarization that is 35 times greater in magnitude than a MEPP. This causes the membrane potential to depolarize +35mV from -100mV to -65mV where it reaches threshold.

Action Potential Phases

Once the membrane potential reaches threshold, an action potential occurs and causes a sharp spike in membrane polarity. There are five phases of an action potential: threshold, depolarization, peak, repolarization, and hyperpolarization.
Threshold is when the summation of MEPPs reaches a certain potential and induces the opening of the ligand gated ion channels. The rapid influx of sodium ions causes the membrane potential to reach a positive charge. The potassium ion channels are slower acting than the sodium ion channels and so as the membrane potential starts to peak, the potassium ion channels open and causes an outflux of potassium to counteract the influx of sodium.
At the peak, the outflux of potassium equals the influx of sodium and the membrane does not change polarity. During repolarization, the sodium channels begin to become inactivated causes a net charge of potassium ions to be leaving the membrane. This causes the membrane potential to drop down to its resting membrane potential of -100mV.
Hyperpolarization occurs because the slow acting potassium channels take long to inactivate and so the membrane overshoots the resting potential. It gradually returns to resting potential and is ready for another action potential to occur.
During the action potential before the hyperpolarization phase, the membrane is unresponsive to any stimulation. This inability to induce another action potential is known as the absolute refractory period. During the hyperpolarization period, the membrane is again responsive to stimulations but it requires a much higher input to induce an action potential. This phase is known as the relative refractory period.
Once the action potential has finished in the neuromuscular junction, the used acetylcholine is cleared out of the synaptic cleft by the enzyme acetylcholine esterase AChEase. 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.

Clinical applications

Current research is attempting to learn more about end plate potentials and their affect on muscle activity. Many current diseases involve disrupted end plate potential activity. In Alzheimer patients, beta amyloid attaches to the acetylcholine receptors and inhibits acetylcholine binding. This causes less signal propagation and small EPPs that do not reach threshold. By analyzing brain processes with acetylcholine, doctors can measure how much beta amyloid is around and use it to judge its affects on Alzheimer’s.
Myasthenia gravis

Myasthenia gravis

Myasthenia gravis is an autoimmune neuromuscular disease leading to fluctuating muscle weakness and fatiguability...

is an autoimmune disease, where the body produces antibodies targeted against the acetylcholine receptor on the postsynaptic membrane in the neuromuscular junction. Muscle fatigue and weakness, worsened with use and improved by rest, is the hallmark of the disease. because of the limited amount of acetylcholine receptors that are available for binding.
Symptomatic treatment consists of using a acetylcholinesterase inhibitor to reduce the breakdown of acetycholine in the neuromuscular junction, so that enough acetylcholine will be present for the small number of unblocked receptors
A congenital abnormality caused by a deficiency in end-plate acetylcholine esterase (AChE) might be a pathophysiologic mechanism for myasthenic gravis. In a study on a patient with AChE deficiency, doctors noted that he had developed severe proximal and truncal muscle weakness with jittering in other muscles. 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.
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. Motor unit potentials are the electrical signals produced by motor units that can be characterized by amplitude, duration, phase, and peak, and the irregularity coefficient (IR) is calculated based on the peak numbers and amplitudes.
Lambert-Eaton myasthenic syndrome

Lambert-Eaton myasthenic syndrome

Lambert–Eaton myasthenic syndrome is a rare autoimmune disorder that is characterised by muscle weakness of the limbs...

is a disorder where presynaptic calcium channels are subjected to autoimmune destruction which causes fewer neurotransmitter vesicles to be exocytosed. This causes smaller EEPs due to less vesicles being released. Oftentimes the smaller EPPs do not reach threshold which causes muscle weakness and fatigue in patients.
Many animals use neurotoxins to defend themselves and kill prey. Tetrodotoxin

Tetrodotoxin

Tetrodotoxin, also known as "tetrodox" and frequently abbreviated as TTX, sometimes colloquially referred to as "zombie powder" by those who practice Vodou, is a potent neurotoxin with no known antidote. There have been successful tests of a possible antidote in mice, but further tests must be...

is a poison found in the certain poisonous fishes such as pufferfish

Pufferfish

Tetraodontidae is a family of primarily marine and estuarine fish of the Tetraodontiformes order. The family includes many familiar species which are variously called pufferfish, balloonfish, blowfish, bubblefish, globefish, swellfish, toadfish, toadies, honey toads, sugar toads, and sea squab...

and triggerfish

Triggerfish

Triggerfishes are about 40 species of often brightly colored fishes of the family Balistidae. Often marked by lines and spots, they inhabit tropical and subtropical oceans throughout the world, with the greatest species richness in the Indo-Pacific...

which blocks the sodium ion channels and prevents an action potential on the postsynaptic membrane. Tetraethylammonium

Tetraethylammonium

Tetraethylammonium is a quaternary ammonium cation consisting of four ethyl groups attached to a central nitrogen atom. Like other members of its class, it can be used to alter a compound's solubility by displacing hard acids with this comparatively softer acid...

found in insects blocks potassium channels. Alpha neurotoxin found in snakes binds to acetylcholine receptors and prevents acetylcholine from binding. Alpha-latrotoxin

Alpha-latrotoxin

α-Latrotoxin can naturally be found in widow spiders of the genus Latrodectus. The most famous of those spiders are the black widows, Latrodectus mactans. The venom of widow spiders contains several protein toxins, called latrotoxins, which selectively target against either vertebrates, insects...

found in black widow spider

Black widow spider

Latrodectus mactans, the Southern black widow, is a highly venomous species of spider in the genus Latrodectus. They are well known for the distinctive black and red coloring of the female of the species and for the fact that she will occasionally eat her mate after reproduction. The species is...

s causes a massive influx of calcium at the axon terminal and leads to an overflow of neurotransmitter release.
Botulinum toxin

Botulinum toxin

Botulinum toxin is a protein produced by the bacterium Clostridium botulinum, and is considered the most powerful neurotoxin ever discovered. Botulinum toxin causes Botulism poisoning, a serious and life-threatening illness in humans and animals...

produced by the bacteria Clostridium botulinum

Clostridium botulinum

Clostridium botulinum is a Gram-positive, rod-shaped bacterium that produces several toxins. The best known are its neurotoxins, subdivided in types A-G, that cause the flaccid muscular paralysis seen in botulism. It is also the main paralytic agent in botox. C. botulinum is an anaerobic...

is the most powerful toxic protein. It prevents release of acetylcholine at the neuromuscular junction by inhibiting docking of the neurotransmitter vesicles.

External links

The source of this article is wikipedia, the free encyclopedia. The text of this article is licensed under the GFDL.

Neuromuscular junction

Acetylcholine

Ion channels

Presynaptic membrane

Postsynaptic membrane

Synaptic Vesicles

Miniature End Plate Potentials (MEPPs)

Threshold potential (“All or nothing”)

Action Potential Phases

Clinical applications

See also

External links