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Unit 2
Action potentials &information conduction and transmission
TOPICS COVERED
The structure of the neuron Membrane potential Features of AP Mechanisms of AP Conduction of AP Myelinated fibers
Information coding in the nervous system Synaptic transmission Neurotransmitters Temporal and spatial summation
UNIT CONTENT Introductory animation about neurons
Neuron Structure The structure of the neuron is designed to sum the input information from other neurons and trigger an action potential that will travel down the axon of the nerve to its destination where it will stimulate the next neuron or cell. Neurons (nerve cells) consist of three main parts:
Soma: the cell body of the neuron where the nucleus is located. Dendrites: tree-like structure of the cell which forms numerous fine connections with other neurons. Information from the previous neuron(s) is integrated in the dendritic tree. Axon: the extension from the soma that transports the action potential to the next neuron(s). The axon makes up the majority of the length of the neuron and may be insulated by a myelin sheath. Axons branch at their ends and each branch eventually terminates at a swelling called the axon terminal.
Synapses, neuronal information transfer sites, occur where axon terminals come in close contact with another nerve cell, a muscle cell, or a gland. The membranes of cells that meet at synapses are called synaptic membranes.In most cases, neurons are stimulated chemically by other neurons that form connections with the dendrites. Neurotransmitters released from the synaptic membrane change the membrane's ion permeability. Many different neurons may form synapses with the dendrites of a single neuron. Some release neurotransmitters that increase the concentration of positively charged ions within the neuron, while others release neurotransmitters that cause the neuron's contents to become more negatively charged. The highly branched dendrites sum the effects of the different synaptic events. If the result is a depolarization (an intracellular increase in the concentration of positive ions) that exceeds the threshold of the neuron, an action potential is generated in a region called the axon hillock, where the axon connects to the cell body. Click here to read about the structure of the neuron
Click here to read about excitable cells This quiz is not graded The Resting Potential:
All cells (not just excitable cells) have a resting potential: an electrical charge across the plasma membrane, with the interior of the cell negative with respect to the exterior. The size of the resting potential varies, but in excitable cells runs about -70 millivolts (mv). The resting potential arises from two activities: The sodium/potassium ATPase. This pump pushes only two potassium ions (K+) into the cell for every three sodium ions (Na+) it pumps out of the cell so its activity results in a net loss of positive charges within the cell. Some potassium channels in the plasma membrane are "leaky" allowing a slow facilitated diffusion of K+ out of the cell (red arrow).
Animation
resting potential Animation
resting potential
Ionic Relations in the Cell
The sodium/potassium ATPase produces: · a concentration of Na+ outside the cell that is some 10 times greater than that inside the cell · a concentration of K+ inside the cell some 20 times greater than that outside the cell. The concentrations of chloride ions (Cl-) and calcium ions (Ca2+) are also maintained at greater levels outside the cell EXCEPT that some intracellular membrane-bound compartments may also have high concentrations of Ca2+ (green oval)
This quiz is not graded Depolarization
Certain external stimuli reduce the charge across the plasma membrane.
In each case, the facilitated diffusion of sodium into the cell reduces the resting potential at that spot on the cell creating an excitatory postsynaptic potential or EPSP. If the potential is reduced to the threshold voltage (about -50 mv in mammalian neurons), an action potential is generated in the cell.
Action Potentials
The nerve impulse. In the resting neuron, the interior of the axon membrane is negatively charged with respect to the exterior (A). As the action potential passes (B), the polarity is reversed. Then the outflow of K+ ions quickly restores normal polarity (C). At the instant pictured in the diagram, the moving spot, which has traced these changes on the oscilloscope as the impulse swept past the intracellular electrode, is at position C.
If depolarization at a spot on the cell reaches the threshold voltage, the reduced voltage now opens up hundreds of voltage-gated sodium channels in that portion of the plasma membrane. During the millisecond that the channels remain open, some 7000 Na+ rush into the cell. The sudden complete depolarization of the membrane opens up more of the voltage-gated sodium channels in adjacent portions of the membrane. In this way, a wave of depolarization sweeps along the cell. This is the action potential (In neurons, the action potential is also called the nerve impulse.)
Animation
- Voltage Gated Channels and the Action Potential Animation Action Potential Animation Action Potential Animation Channel Gaiting during an Action Potential
Sodium - potassium Pump
Animation Sodium-potassium pump Animation - Sodium-potassium pump
The refractory period
A second stimulus applied to a neuron (or muscle fiber) less than 0.001 second after the first will not trigger another impulse. The membrane is depolarized (position B above), and the neuron is in its refractory period. Not until the -70 mv polarity is reestablished (position C above) will the neuron be ready to fire again. Repolarization is first established by the facilitated diffusion of potassium ions out of the cell. Only when the neuron is finally rested are the sodium ions that came in at each impulse actively transported back out of the cell. In some human neurons, the refractory period lasts only 0.001-0.002 seconds. This means that the neuron can transmit 500-1000 impulses per second.
The action potential is all-or-none
The strength of the action potential is an intrinsic property of the cell. So long as they can reach the threshold of the cell, strong stimuli produce no stronger action potentials than weak ones. However, the strength of the stimulus is encoded in the frequency of the action potentials that it generates.
Myelinated Neurons
The axons of many neurons are encased in a fatty sheath called the myelin sheath. It is the greatly expanded plasma membrane of an accessory cell called the Schwann cell. Where the sheath of one Schwann cell meets the next, the axon is unprotected. The voltage-gated sodium channels of myelinated neurons are confined to these spots (called nodes of Ranvier).
The inrush of sodium ions at one node creates just enough depolarization to reach the threshold of the next. In this way, the action potential jumps from one node to the next. This results in much faster propagation of the nerve impulse than is possible in nonmyelinated neurons.
Myelinated versus unmyelinated axons
Animation Salutatory Conduction Animation - Action Potential Propagation in
an Unmyelinated Axon Animation - Salutatory Conduction
Multiple sclerosis
This autoimmune disorder results in the gradual destruction of myelin sheaths. Despite this, transmission of nerve impulses continues for a period as the cell inserts additional voltage-gated sodium channels in portions of the membrane formerly protected by myelin.
A nice lecture on Multiple sclerosis
interesting but optional
A
nice video on Multiple sclerosis shorter than the one above and worth
watching Go to 3D Medical Animations,
select Multiple sclerosis from topics (left corner of the video screen)
notice that you have the options of - Video, Text, Model and Slides.
Hyperpolarization
Despite their name, some neurotransmitters inhibit the transmission of nerve impulses. They do this by opening
In each case, opening of the channels increases the membrane potential by
This hyperpolarization is called an inhibitory postsynaptic potential (IPSP). Although the threshold voltage of the cell is unchanged, it now requires a stronger excitatory stimulus to reach threshold.
Example: Gamma amino butyric acid (GABA). This neurotransmitter is found in the brain and inhibits nerve transmission by both mechanisms: ·
The physical factors behind the Action
Potential
Animations about Action potentials This will help you understand the graphs Required QUIZ 1 Unit 2 Please take in : www.uh.edu/webct You will have 40 minutes to complete the Required Quiz - use your time wisely!
Synaptic transmission
Animations of Synaptic
transmission The process by which this information is communicated is called synaptic transmission and can be broken down into four steps.
First, the neurotransmitter must be synthesized and stored in vesicles so that when an action potential arrives at the nerve ending, the cell is ready to pass it along to the next neuron.
Next, when an action potential does arrive at the terminal, the neurotransmitter must be quickly and efficiently released from the terminal and into the synaptic cleft.
The neurotransmitter must then be recognized by selective receptors on the postsynaptic cell so that it can pass along the signal and initiate another action potential. Or, in some cases, the receptors act to block the signals of other neurons also connecting to that postsynaptic neuron.
After its recognition by the receptor, the neurotransmitter must be inactivated so that it does not continually occupy the receptor sites of the postsynaptic cell. Inactivation of the neurotransmitter avoids constant stimulation of the postsynaptic cell, while at the same time freeing up the receptor sites so that they can receive additional neurotransmitter molecules, should another action potential arrive.
MORE DETAILS: The first step in synaptic transmission is the synthesis and storage of neurotransmitters. There are two broad categories of neurotransmitters. Small-molecule neurotransmitters are synthesized locally within the axon terminal. Some of the precursors necessary for the synthesis of these molecules are taken up by selective transporters on the membrane of the terminal. Others are byproducts of cellular processes that take place within the neuron itself and are thus readily available. The enzymes necessary to catalyze an interaction among these precursors are usually produced in the cell body and transported to the terminal by slow axonal transport. Acetylcholine (ACh), is an example of an excitatory small-molecule neurotransmitter. This important, well-studied neurotransmitter, made up of choline and acetate, is found at various locations throughout the central and peripheral nervous systems and at all neuromuscular junctions. The synthesis of ACh requires the enzyme choline actyltransferase and, like all small-molecule neurotransmitters, takes place within the nerve terminal. Neuropeptides are the second category of neurotransmitters. These messengers differ from small-molecule neurotransmitters in both size and in the way that they are synthesized. Neuropeptides generally range from 3 to 36 amino acids in length, and are thus larger than small-molecule neurotransmitters. Also, neuropeptides must made in the cell body because their synthesis requires peptide bond formation. This process is a great deal more involved than the simple enzymatic reactions involved in making smaller neurotransmitters. The synthesis of a neuropeptide is very much like the synthesis of any secretory protein made by the cell. First, within the cell nucleus, gene transcription takes place, during which a specific peptide-coding sequence of DNA is used as a template to construct a corresponding strand of messenger RNA. The mRNA then travels to a ribosome, where the process of translation begins. During translation, the sequence of nucleotides that make up the mRNA act as a code to string together a corresponding sequence of amino acids that will eventually become the neuropeptide needed at the terminal. Before this molecule can be transported to the terminal for release into the synaptic cleft, it must be processed in the endoplasmic reticulum (ER), packaged in the golgi apparatus, and transported in storage vesicles down the axon to the terminal. The endogenous opioids, a large family of neuropeptides that act as natural analgesics, provide a good example of how post-translational processing of just one precursor molecule can result in a whole spectrum of different, but related, neurotransmitters. Selective cleaving and splicing of each just three precursor molecules results in the production of the various opioids included in this family of neurotransmitters. Once they are synthesized, neurotransmitters, both small molecules and neuropeptides, are stored in vesicles within the axon terminal until an action potential arrives and they are released. Most small-molecule neurotransmitters are stored in small vesicles that range from 40 to 60 nm in diameter and, in electron micrographs, appear to have clear centers. The vesicles that store neuropeptides are larger, ranging from 90 to 250 nm in diameter. These vesicles appear dark and electron-dense in electron micrographs. For a table of small molecule
neurotransmitters and their site of synthesis, go to http://web.indstate.edu/thcme/mwking/nerves.html#table
At rest, neurotransmitter-containing vesicles are stored at the terminal of the neuron in one of two places. A small number of vesicles are positioned along the pre-synaptic membrane in places called "active zones." This is where neurotransmitter release occurs. Most vesicles, however, are held close to these zones, yet further from the membrane itself until they are needed. These vesicles are held in place by Ca2+-sensitive vesicle membrane proteins (VAMPs), which bind to actin filaments, microtubules, and various other elements of the cytoskeleton. When an action potential reaches the terminal of a presynaptic neuron, voltage-dependent calcium (Ca2+) channels embedded in the pre-synaptic membrane open and Ca2+ rushes in. This influx of calcium ions triggers a series of events, which ultimately results in the release of the neurotransmitter from a storage vesicle into the synaptic cleft. The first step in this process involves freeing the neurotransmitter-containing vesicles from the bonds that hold them to the cytoskeleton. The vesicles are then free to travel to the active zones, where docking takes place. Docking is the process by which the vesicle and the pre-synaptic membrane line up in a position that will allow them to fuse easily. Fusion then takes place, in which the vesicle membrane and the pre-synaptic membrane connect to form a small opening, a pore, connecting the lumen of the vesicle with the synaptic cleft. This pore grows larger and larger until the vesicle membrane collapses into the pre-synaptic membrane and releases its contents into the synaptic cleft, a process called exocytosis. Following exocytosis, the vesicular membrane, presently a continuous extension of the pre-synaptic membrane, forms a pit and pinches off into the terminal to form a new, vacant vesicle. This vesicle is then either recycled and refilled with more of the neurotransmitter, or sent to the cell body, where it is broken down, processed into a new vesicle, and transported to the terminal where it can then be filled with the neurotransmitter. After release into the synaptic cleft, neurotransmitters interact with receptor proteins on the membrane of the postsynaptic cell, causing ionic channels on the membrane to either open or close. When these channels open, depolarization occurs, resulting in the initiation of another action potential. There are two types of postsynaptic receptors that recognize neurotransmitters. Ionotropic receptors, also referred to as ligand-gated ion channels, act quickly to depolarize the neuron and pass on the action potential (or hyperpolarize the neuron and inhibit additional action potentials). These receptors are made up of five individual protein subunits embedded in the cell membrane, and arranged to form a single pore th at spans this membrane. When a neurotransmitter associates with the extracellular recognition site, the membrane-spanning subunits of the receptor quickly open to form a pore through which the necessary ions can pass. Depolarization usually occurs a m illisecond or two after the action potential has been received and lasts only up to ten milliseconds. Gamma-aminobutyric acid (GABA) is one example of a neurotransmitter recognized by an ionotropic receptor. GABA is an inhibitory neurotransmitter used at roughly one-third of the synapses in the brain. The binding of GABA at the GABA recognition site causes the membrane-spanning channel of the receptor protein to open and allow an influx of negatively charged chloride ions. This influx of negative ions serves to hyperpolarize the cell thus inhibiting the firing of an action potential. Though in the case of GABA, the ionotropic receptor is used to inhibit the firing of an action potential, there are other ionotropic receptors which recognize excitatory neurotransmitters and thus stimulate the firing of action potentials in post-synaptic cells. Metabotropic receptors, or G-protein linked receptors, do not work as simply as ligand-gated ion channels do. Like ionotropic receptors, metabotropic receptors also have an extracellular neurotransmitter recognition site, yet these receptors do not form a membrane-spanning pore that can allow the direct passage of ions. Instead, when a neurotransmitter associates with the extracellular recognition site, an intermediate molecule within the postsynaptic cell, called a G-protein, is activated and, either directly or through a series of enzymatic reactions, opens or closes ion channels located at other places on the cell membrane. Because the action of metabotropic recepto rs is not as direct, their action is slower. Depolarization takes longer, typically lasting up to hundreds of milliseconds, and in some cases, going on for several minutes, hours, or even days. Metabotropic receptors are used in the recognition of all neuropeptides and several small-molecule neurotransmitters. Dopamine (DA), for example, is a small-molecule neurotransmitter recognized by a G-protein coupled receptor. The binding of DA a t the recognition site of a post-synaptic DA receptor sets off a chain of reactions which ultimately cause ion pores along the post-synaptic membrane to open and an action potential to be stimulated. Found in four major tracts of the brain (the nigrostri al tract, the tuberoinfundibular tract, the mesolimbic tract, and the mesocortical tract), DA plays an important role in the control of both motor and emotional behavior. After a neurotransmitter molecule has been recognized by a post-synaptic receptor, it is released back into the synaptic cleft. Once in the synapse, it must be quickly removed or chemically inactivated in order to prevent constant stimulation of the post-synaptic cell and an excessive firing of action potentials. Some neurotransmitters are removed from the synaptic cleft by special transporter proteins on the pre-synaptic membrane. These transporter proteins carry the neurotransmitter back into the pre-synaptic cell, where it is either re-packaged into a vesicle and stored until it is once again needed to transmit a chemical message, or broken down by enzymes. Serotonin is one neurotransmitter that gets recycled in this way. Serotonin, a small-molecule neurotransmitter found in many areas throughout the brain, is involved in a wide range of behaviors, including sleep, appetite, memory, sexual behavior, neuroendocrine function, and mood. Not all neurotransmitters are recycled by the presynaptic cell. Neuropeptide neurotransmitters merely quickly diffuse away from the receptors into the surrounding medium. One important neurotransmitter, acetylcholine, has a specialized enzyme for inactivation right in the synaptic cleft called acetylcholinesterase (AChE. AChE is an enzyme present at all cholinergic synapses which serves to inactivate acetylcholine by hydrolysis. Acetylcholine (ACh), an excitatory small-molecule neurotransmitter found at various locations throughout the central and peripheral nervous systems and at all neuromuscular junctions, is composed of acetate and choline. AChE breaks ACh into its component parts; acetate and choline. After hydrolysis, acetate quickly diffuses into the surrounding medium, while choline gets taken back into the presynaptic cell by a high affinity choline uptake (HACU) system. Choline is then recycled by the pre-synaptic cell for use in the synthesis of more ACh. TEMORAL and SPATIAL SUMMATION Summation of excitation and inhibition is the vital principle on which the functioning of the CNS is based. The principle of summation relates to the fact that a neuron typically has a large number of synaptic terminals (boutons) ending upon it. Alone, each bouton is capable of producing a only a small synaptic potential. The small excitatory post-synaptic potential (EPSP) produced by a single excitatory terminal is not sufficient to depolarize the motor neuron to its threshold point. For suprathreshold depolarization to be produced, either temporal or spatial summation must take place.
Required QUIZ Unit 2 Please take in : www.uh.edu/webct You will have 23 minutes to complete the Required Quiz - use your time wisely! |
