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Neurochemistry: Neuron Functions

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Define the permeability of cell membranes
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Cell membranes act as a wall and gate keeper. They are semi-permeable because the cell needs to import and export materials.
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Define semi-permeability of cell membranes
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Cell membranes are lipophilic so non polar compounds can go through the membrane. However, polar compounds and ions cannot.
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How do polar molecules get through the membranes?
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They get through using membrane-bound protein structures called transmembrane proteins: ions are transported in and out that way. Protons use proton pumps.
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What is the use of channels and gates in neurons?
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Neurons use ion gates for example to convey information from one neuron to another. Information is an electrical energy changed from chemical energy.
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Define a concentration gradient.
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A concentration gradient is the gradual difference in concentration of a dissolved substance in a solution between a region of high concentration and one of lower concentration. In the end, the substance will be evenly dispersed meaning that the system will have reached equilibrium. Example: You add a drop of food dye to water in a glass. It starts with most of the dye in one area around where the drop entered the water and gradually because of the kinetic energy of water molecules and molecular motion, the dye molecules disperse in the rest of the water.
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Define voltage and voltage gradient.
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Voltage is defined as electric tension or electric potential difference. Simply, it is the difference in electric potential energy between two points per unit electric charge in a circuit. An electrochemical gradient (or voltage gradient) is a gradient of electrochemical potential, usually for an ion that can move across a membrane. The gradient consists of two parts, the chemical gradient, or difference in solute concentration across a membrane, and the electrical gradient, or difference in charge across a membrane.
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How does a voltage gradient or electrochemical gradient work?
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When there are unequal concentrations of an ion across a permeable membrane, the ion will move across the membrane from the area of higher concentration to the area of lower concentration through simple diffusion. Ions also carry an electric charge that forms an electric potential across a membrane. If there is an unequal distribution of charges across the membrane, then the difference in electric potential generates a force that drives ion diffusion until the charges are balanced on both sides of the membrane.
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Define depolarization.
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Depolarization is a change within a cell, during which the cell undergoes a shift in electric charge distribution, resulting in less negative charge inside the cell.
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Define cell membrane potential.
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Most cells in higher organisms maintain an internal environment that is negatively charged relative to the cell’s exterior. This difference in charge is called the cell’s membrane potential.
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Define action potential.
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The action potential is a short-lasting event during 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. In neurons, action potentials play a central role in cell-to-cell communication by providing for or assisting in (with regard to salt ion conduction), the propagation of signals along the neuron’s axon towards boutons at the axon ends which can then connect with other neurons at synapses, or to motor cells or glands.
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What happens during depolarization?
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The negative internal charge of the cell temporarily becomes more less negative or more positive. This change from a negative to a more positive membrane potential occurs during several processes, including an action potential. During an action potential, the depolarization is so large that the potential difference across the cell membrane briefly reverses polarity, with the inside of the cell becoming positively charged.
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What are voltage-gated channels?
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Voltage-gated ion channels are a type of transmembrane proteins that act as ion channels activated by changes in the electrical membrane potential near the channel. The membrane potential alters the conformation of the channel proteins, regulating opening and closing.
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What is the Hodgkin-Huxley model?
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The Hodgkin-Huxley model models neuron cell membranes. It is a mathematical model that describes how action potentials in neurons are initiated and propagated. It is a set of nonlinear differential equations that approximates the electrical characteristics of excitable cells like neurons.
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Explain the principles of a voltage-gradient across a neuron cell membrane using an experimental set up with sodium and chloride ions.
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1. Beaker of water with a semi-permeable membrane separating the beaker into 2 areas. 2. NaCl salt is placed in one of the areas. 3. The semi-permeable membrane allows the Cl- ions to pass through to the other side but not Na+ ions. Cl- will diffuse from the side with greater concentration to the area with lower concentration of Cl-. 4. Cl- will not be equally distributed in both areas because the voltage gradient pulls the Cl- ions back on the side where the Na+ are located. 5. At equilibrium, the side with the Na+ ions will be positively charged because there are more Na+ ions than Cl- ions. The other side will be negatively charged since it only contais Cl- ions. At this point the concentration gradient= voltage gradient. 6. The voltage difference will be the greatest near the membrane.
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Why is the voltage difference the greatest near the membrane?
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The voltage difference can be explained by the energy of interaction (the energy required to separate 2 charged particles). U= q1q2/e*r where U= energy of interaction, q1 and q2 are the particles charges, r is the distance, e is the dielectric constant of the medium (water). Attraction is always negative= attraction. The magnitude of the attraction or the energy of interaction depends on the distance of separation (inversely proportional).
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What is a resting potential in a neuron?
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When a neuron is not sending a signal, it is “at rest.” When a neuron is at rest, the inside of the neuron is negative relative to the outside. Although the concentrations of the different ions attempt to balance out on both sides of the membrane, they cannot because the cell membrane allows only some ions to pass through channels (ion channels).
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Difference between resting and action potential.
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The resting potential tells about what happens when a neuron is at rest. An action potential occurs when a neuron sends information down an axon, away from the cell body.
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Give more details about the resting potential.
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At rest, potassium ions (K+) can cross through the membrane easily. Also at rest, chloride ions (Cl-)and sodium ions (Na+) have a more difficult time crossing. The negatively charged protein molecules inside the neuron cannot cross the membrane. In addition to these selective ion channels, there is a pump that uses energy to move three sodium ions out of the neuron for every two potassium ions it puts in. Finally, when all these forces balance out, and the difference in the voltage between the inside and outside of the neuron is measured, you have the resting potential. The resting membrane potential of a neuron is about -70 mV. This means that the inside of the neuron is 70 mV less than the outside. At rest, there are relatively more sodium ions outside the neuron and more potassium ions inside that neuron.
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Why is the inside of the cell still more negative if K+ ions are more numerous?
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Even though K+ is 20X more numerous inside the cell than outside, it still does not out number the negative proteins present inside the cell. The resting potential is maintained by the ratio of K+ to protein molecules. If more K+ ions moved inside the cell, they will be pumped out.
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How is the concentration of Na+ kept higher on the outside of the cell? Wouldn’t Na+ get inside the cell at some point?
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Na+ ions are not free to move across the membrane. If they did, they would render the inside of the cell more positive. Na+/K+ ion pump exists that keeps Na+ ions out and K+ ions in. The Na+/K+ ion pump is a protein embedded inside the cell membrane. A neuron membrane contains several thousands pumps working to transport 3 Na+ ions out and 2 K+ in.
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What is the function of Cl- ions in the resting potential?
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Cl- freely go in and out of the cell membrane, through the chloride ion channels. At equilibrium Cl- ion concentration gradient equals the Cl- ion voltage gradient at around the cell membrane resting potential.
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Define a graded potential.
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Graded potentials are changes in membrane potential that vary in size, as opposed to being all-or-none. They arise from the summation of the individual actions of ligand-gated ion channel proteins, and decrease over time and space.
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Define synaptic or synapse.
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A synapse is a region where nerve impulses are transmitted and received, encompassing the axon terminal of a neuron that releases neurotransmitters in response to an impulse, an extremely small gap across which the neurotransmitters travel, and the adjacent membrane of an axon, dendrite, or muscle or gland cell with the appropriate receptor molecules for picking up the neurotransmitters.
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Define post-synaptic neuron.
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The post-synaptic neuron is the nerve cell on the receiving end of an electrical impulse from a neighboring cell. The pre-synaptic, “sender” neuron releases neurotransmitters that attach themselves to receptors on the dendrites (or arms) of the post-synaptic, “receiver” neuron. The post-synaptic neuron does not accept all neurotransmitters, only those that fit in or match its receptors. The signals received by the post-synaptic neuron tell it whether or not to fire its own electrical impulse and send communication to another cell.
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What is an Excitatory postsynaptic potential (EPSP)?
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An excitatory postsynaptic potential (EPSP) is a postsynaptic potential that makes the post synaptic neuron more likely to fire an action potential. This temporary depolarization of postsynaptic membrane potential, caused by the flow of positively charged ions into the postsynaptic cell, is a result of opening ligand-gated ion channels.
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What is an inhibitory postsynaptic potential (IPSP)?
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An inhibitory postsynaptic potential (IPSP) is a kind of synaptic potential that makes a postsynaptic neuron less likely to generate an action potential. Another way to look at inhibitory postsynaptic potentials is that they are also a chloride conductance change in the neuronal cell because it decreases the driving force. They can take place at all chemical synapses, which use the secretion of neurotransmitters to create cell to cell signalling. Inhibitory presynaptic neurons release neurotransmitters that then bind to the postsynaptic receptors; this induces a postsynaptic conductance change as ion channels open or close. An electric current that changes the postsynaptic membrane potential to create a more negative postsynaptic potential is generated.
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Give factors that play a role in IPSP?
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1). Size of the neurons. Postsynaptic potentials are summed and occur in smaller neurons, whereas in larger neurons larger numbers of synapses and ionotropic receptors as well as a longer distance from the synapse to the soma enables the prolongation of interactions between neurons. 2) Inhibitory molecules like GABA. GABA receptors are pentamers most commonly composed of three different subunits (α, β, γ), although several other subunits (δ,ε, θ, π, ρ) and conformations exist. The open channels are selectively permeable to chloride or potassium ions (depending on the type of receptor) and allow these ions to pass through the membrane. If the electrochemical potential of the ion is more negative than that of the action potential threshold then the resultant conductance change that occurs due to the binding of GABA to its receptors keeps the postsynaptic potential more negative than the threshold and decreases the probability of the postsynaptic neuron completing an action potential. Glycine molecules and receptors work much in the same way in the spinal cord, brain, and retina. 3) Ionotropic receptors or ligand-gated ion channel) play an important role in inhibitory postsynaptic potentials. A neurotransmitter binds to the extracellular site and opens the ion channel that is made up of a membrane-spanning domain that allows ions to flow across the membrane inside the postsynaptic cell. This type of receptor produces very fast postsynaptic actions within a couple of milliseconds of the presynaptic terminal receiving an action potential. These channels influence the amplitude and time-course of postsynaptic potentials as a whole. Ionotropic GABA receptors are used in binding for various drugs such as barbiturates (Phenobarbital, pentobarbital), steroids, and picrotoxin. Benzodiazepines (Valium) bind to the α and δ subunits of GABA receptors in order to improve GABAergic signaling. Alcohol also modulates ionotropic GABA receptors.
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Give details on the action potential.
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An action potential occurs when a neuron sends information down an axon, away from the cell body. Neuroscientists use other words, such as a “spike” or an “impulse” for the action potential. The action potential is an explosion of electrical activity that is created by a depolarizing current. This means that some event (a stimulus) causes the resting potential to move toward 0 mV. When the depolarization reaches about -50-55 mV, a neuron is ready to fire an action potential. This is the threshold potential. If the neuron does not reach this critical threshold level, then no action potential will fire. Also, when the threshold level is reached, an action potential of a fixed sized will always fire…for any given neuron, the size of the action potential is always the same. There are no big or small action potentials in one nerve cell – all action potentials are the same size. Therefore, the neuron either does not reach the threshold or a full action potential is fired – this is the “ALL OR NONE” principle. Action potentials are caused when different ions cross the neuron membrane. A stimulus first causes sodium channels to open. Because there are many more sodium ions on the outside, and the inside of the neuron is negative relative to the outside, sodium ions rush into the neuron. Remember, sodium has a positive charge, so the neuron becomes more positive and becomes depolarized. It takes longer for potassium channels to open. When they do open, potassium rushes out of the cell, reversing the depolarization. Also at about this time, sodium channels start to close. This causes the action potential to go back toward -70 mV (a repolarization). The action potential actually goes past -70 mV (a hyperpolarization) because the potassium channels stay open a bit too long. Gradually, the ion concentrations go back to resting levels and the cell returns to -70 mV.
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Role of Voltage-Gated Ion Channels
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Voltage-gated ion channels that are selectively permeable to each of the major physiological ions—Na+, K+, Ca2+, and Cl-. Other electrical responses in neurons are due to the activation of voltage-gated Ca2+ channels. In some neurons, voltage-gated Ca2+ channels give rise to action potentials in much the same way as voltage-sensitive Na+ channels. In many other neurons, Ca2+ channels can control the shape of action potentials generated primarily by Na+ conductance changes. By affecting intracellular Ca2+ concentrations, the activity of Ca2+ channels regulates an enormous range of biochemical processes within cells. Perhaps the most important of the processes regulated by voltage-sensitive Ca2+ channels is the release of neurotransmitters at synapses (see Chapter 5). Given these crucial functions, it is perhaps not surprising that 16 different Ca2+ channel genes have been identified. Like Na+ channels, different Ca2+ channels differ in their activation and inactivation properties, allowing subtle variations in both electrical and chemical signaling processes mediated by Ca2+. As a result, drugs that block voltage-gated Ca2+ channels are especially valuable in treating a variety of conditions ranging from heart disease to anxiety disorders.
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What are refractory periods?
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A refractory period is a period of time during which an organ or cell is incapable of repeating a particular action, or (more precisely) the amount of time it takes for an excitable membrane to be ready for a second stimulus once it returns to its resting state following an excitation. It most commonly refers to electrically excitable muscle cells or neurons. Absolute refractory period corresponds to depolarization and repolarization, whereas relative refractory period corresponds to hyperpolarization.
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What is meant by poisoning the action potential?
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Tetrodotoxin (TTX) is a naturally-found poison that inhibits the voltage-gated Na+ channels. It is found in the liver and sex organs of marine puffer fish and other species of the order Tetraodontiformes (which includes porcupinefish, ocean sunfish, and triggerfish). Tetrodotoxin has also been found in other animals including the blue-ringed octopus and rough-skinned newt. It is interesting to note that TTX is actually produced by symbiotic bacteria living within the above-mentioned animals. Interestingly, puffer fish is a delicacy in some countries and, therefore, the ovaries must be carefully and completely removed before puffer fish is served. If done incorrectly, even minute quantities of ingested TTX can be fatal! Because of its ability to block action potentials and, hence, interfere with, or severely disrupt, the function of the nervous system, TTX is also considered to be a neurotoxin. Indeed, TTX can bind to voltage-gated Na+ channels at very low concentrations (nanomolar range). Poisoning at low levels, such as when ingesting improperly prepared puffer fish, can lead to numbness and/or tingling of the tongue. Moderate levels of TTX can lead to disturbances of the heart rhythm. Poisoning at high concentrations can paralyze the diaphragm leading to asphyxia and death. Local anesthetics such as lidocaine (Xylocaine®) and procaine (Novacaine®) prevent the generation of action potentials by inhibiting voltage-gated Na+ channels of sensory neurons. Thus, depolarization elicited by sensory stimulation (generator or receptor potentials) does not lead to the generation of action potentials that can travel to the central nervous system. Lidocaine and procaine are commonly referred to as nerve blocking agents and, as we have mentioned, the molecular basis of their action is inhibition of the voltage-gated Na+ channels. Similarly, voltage-gated K+ channels can be inhibited by specific agents. Tetraethyl ammonium (TEA), a quaternary ammonium cation, is one such agent that inhibits the voltage-gated K+ channels of neurons. As a blocker of voltage-gated K+ channels, TEA is very useful in elucidating the role K+ channels play in the neuronal action potential
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Summarize the action potential.
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1) The depolarization, also called the rising phase, is caused when positively charged sodium ions (Na+) suddenly rush through open voltage-gated sodium channels into a neuron. As additional sodium rushes in, the membrane potential actually reverses its polarity. During this change of polarity the membrane actually develops a positive value for a moment (+40 millivolts). 2) The repolarization or falling phase is caused by the slow closing of sodium channels and the opening of voltage-gated potassium channels. As a result, the membrane permeability to sodium declines to resting levels. As the sodium ion entry declines, the slow voltage-gated potassium channels open and potassium ions rush out of the cell. This expulsion acts to restore the localized negative membrane potential of the cell. 3) Hyperpolarization is a phase where some potassium channels remain open and sodium channels reset. A period of increased potassium permeability results in excessive potassium efflux before the potassium channels close. This results in hyperpolarization as seen in a slight dip following the spike.
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What is the propagation of the action potential?
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The propagation of action potential is independent of stimulus strength but dependent on refractory periods. The period from the opening of the sodium channels until the sodium channels begin to reset is called the absolute refractory period. During this period, the neuron cannot respond to another stimulus, no matter how strong.
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Define what a nerve impulse is.
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Nerve impulses have a domino effect. Each neuron receives an impulse and must pass it on to the next neuron and make sure the correct impulse continues on its path. Through a chain of chemical events, the dendrites (part of a neuron) pick up an impulse that’s shuttled through the axon and transmitted to the next neuron. The entire impulse passes through a neuron in about seven milliseconds — faster than a lightning strike.
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Summary of a nerve impulse steps
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1) Polarization of the neuron’s membrane: Sodium is on the outside, and potassium is on the inside. 2) Resting potential gives the neuron a break. 3) Action potential: Sodium ions move inside the membrane. 4) Repolarization: Potassium ions move outside, and sodium ions stay inside the membrane. 5) Hyperpolarization: More potassium ions are on the outside than there are sodium ions on the inside. 6) Refractory period puts everything back to normal: Potassium returns inside, sodium returns outside. 7) Calcium gates open. At the end of the axon from which the impulse is coming, the membrane depolarizes, gated ion channels open, and calcium ions (Ca2+) are allowed to enter the cell. 8) Releasing a neurotransmitter. When the calcium ions rush in, a chemical called a neurotransmitter is released into the synapse. 9) The neurotransmitter binds with receptors on the neuron. The chemical that serves as the neurotransmitter moves across the synapse and binds to proteins on the neuron membrane that’s about to receive the impulse. The proteins serve as the receptors, and different proteins serve as receptors for different neurotransmitters — that is, neurotransmitters have specific receptors. 10) Excitation or inhibition of the membrane occurs. Whether excitation or inhibition occurs depends on what chemical served as the neurotransmitter and the result that it had. For example, if the neurotransmitter causes the Na+ channels to open, the neuron membrane becomes depolarized, and the impulse is carried through that neuron. If the K+ channels open, the neuron membrane becomes hyperpolarized, and inhibition occurs. The impulse is stopped dead if an action potential cannot be generated. After the neurotransmitter produces its effect, whether it’s excitation or inhibition, the receptor releases it and the neurotransmitter goes back into the synapse. In the synapse, the cell “recycles” the degraded neurotransmitter. The chemicals go back into the membrane so that during the next impulse, when the synaptic vesicles bind to the membrane, the complete neurotransmitter can again be released.
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What are Schwann cells?
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There are two types of Schwann cell, myelinating and nonmyelinating. Myelinating Schwann cells wrap around axons of motor and sensory neurons to form the myelin sheath. The Schwann cell promoter is present in the downstream region of the human dystrophin gene that gives shortened transcript that are again synthesized in a tissue specific manner. During the development of the peripheral nervous system, the regulatory mechanisms of myelination are controlled via feedforward interaction of specific genes, influencing transcriptional cascades and shaping the morphology of the myelinated nerve fibers. Schwann cells are involved in many important aspects of peripheral nerve biology—the conduction of nervous impulses along axons, nerve development and regeneration, trophic support for neurons, production of the nerve extracellular matrix, modulation of neuromuscular synaptic activity, and presentation of antigens to T-lymphocytes. Myelin inhibits electrical conduction. So neurons are not all the way covered with myelin. There are ares very rich in channels called the nodes of Ranvier that will allow the conduction of electrical impulses.