2. exitable 2-08-09


Published on

Published in: Business, Lifestyle
  • Be the first to comment

  • Be the first to like this

No Downloads
Total views
On SlideShare
From Embeds
Number of Embeds
Embeds 0
No embeds

No notes for slide

2. exitable 2-08-09

  2. 2. TIME CONSTANT <ul><ul><li>One of the characteristics of the nervous system is its ability to transfer information very rapidly in the form of changes in the transmembrane potential from one part of the system to another. It is very important to know, how this electrical information is able to move along nerve fibers. </li></ul></ul><ul><ul><li>Let us consider a nerve fiber that contains only leakage channels, not voltage-sensitive channels. At position (x = 0) two electrodes penetrate the nerve, one to record the transmembrane potential and the second to inject current. </li></ul></ul>
  3. 3. TIME CONSTANT <ul><li>If a square pulse of depolarizing current is injected at position x = 0 at time = 0, an electrotonic , depolarizing response is measured by the recording electrode. </li></ul><ul><li>It takes some time (20 msec) for the transmembrane potential to stabilize at its final value of -60 mV. This depolarization will last as long as the current is injected into the cell. </li></ul><ul><li>The speed of achieving this final potential depends on the resistance and capacitive properties of the membrane. </li></ul><ul><li>The time constant is the time it takes the transmembrane potential to achieve 63% of its final value. </li></ul>
  4. 4. SPACE CONSTANT <ul><ul><li>Two additional recording electrodes are placed inside the nerve 2.5 mm (green electrode) and 5.0 mm (red electrode) from the electrode used to inject the current. </li></ul></ul><ul><ul><li>The maximum potential change takes place at the point of stimulation (blue electrode and blue voltage vs. time tracing). </li></ul></ul><ul><ul><li>As the distance between the stimulating and recording electrodes increases, the maximum voltage response to the current pulse decreases. </li></ul></ul>
  5. 5. SPACE CONSTANT <ul><li>A measure of how the maximal potential change decreases with distance from the point of current injection is the length constant . </li></ul><ul><li>It is the distance over which the maximal potential change decays by 63% to 37% of its value at the point of stimulation. </li></ul><ul><li>At this distance from the stimulating electrode, the maximum change in potential (10 mV, from -60 to -70 mV) has decayed by 63%. </li></ul>
  6. 6. SPACE CONSTANT: DEFINITION <ul><li>The membrane of this cell has no voltage-sensitive channels, so its response to stimulation is electrotonic . Therefore, the process by which this electrotonic response carries information from one area of the cell to another is referred to as electrotonic conduction. </li></ul><ul><li>The magnitude of the response decays very rapidly with distance from the initial point of the voltage change, so this type of conduction can only be used to carry information over very short distances. </li></ul><ul><li>Electrotonic responses occur in the nerve-ending regions of receptor cells, dendrites, and in the internodal regions of myelinated nerve fibers. </li></ul>
  7. 7. ELECTROTONIC CONDUCTION: MEMBRANE CURRENT FLOW <ul><ul><li>Why does the transmembrane potential response decay so rapidly with distance in electrotonic conduction? </li></ul></ul><ul><ul><li>When current is injected at a point along a nerve fiber, the injected charge changes the charge on the membrane capacitance at that point and, thereby, changes the transmembrane potential. However, all the injected charge does not remain at the site of injection. The resistance of the intracellular medium allows the current to flow down the longitudinal axis of the nerve fiber, carrying charge to other regions of the nerve. </li></ul></ul>
  8. 8. ELECTROTONIC CONDUCTION: MEMBRANE CURRENT FLOW <ul><li>The membrane has ionic leakage channels through which some of this charge will return to the current generator. This leaves less charge to change the charge on the membrane capacitance at distant locations. </li></ul><ul><li>As a result, the maximum change in the transmembrane potential decays symmetrically on either side of the point of current injection in response to a square current pulse. </li></ul>
  9. 9. ELECTROTONIC CONDUCTION: EFFECTS OF CHANGING MEMBRANE CAPACITANCE <ul><ul><li>Any changes in membrane properties that allow more charge from an injected current to reach distant points along the nerve fiber increase the space constant. </li></ul></ul><ul><ul><li>Decreasing membrane capacitance, decreasing conductance of the leakage channels, and decreasing axoplasmic resistance increase the space constant. </li></ul></ul>
  10. 10. ELECTROTONIC CONDUCTION: EFFECTS OF CHANGING MEMBRANE CONDUCTANCE <ul><ul><li>The space constant increases with any change that allows more charge to reach distant points along the nerve fiber: decreasing conductance of the membrane leakage channels. </li></ul></ul><ul><ul><li>If the conductance of the leakage channels decreases, less charge from the injected current leaks through them back to the current source. This leaves more charge within the cell to change the charge on the capacitance of distant parts of the nerve fiber. The conductance of the leakage channels does not change in response to electrical stimulation. However, myelination of a nerve effectively decreases the conductance of the membrane, increases the space constant of myelinated nerve fibers. </li></ul></ul>
  11. 11. ELECTROTONIC CONDUCTION: EFFECTS OF CHANGING INTRACELLULAR RESISTANCE <ul><ul><li>The axoplasmic resistance of the nerve fiber and the resistance of the leakage channels are arranged in parallel. As a result, charge from the injected current is divided between traveling down the longitudinal axis of the fiber and out of the cell through the leakage channels. </li></ul></ul><ul><ul><li>A decrease in axoplasmic resistance allows more current to flow down the longitudinal axis of the fiber and provides more charge to distant regions of the nerve fiber. As a result, the space constant increases . As the diameter of a fiber increases, axoplasmic resistance decreases. </li></ul></ul><ul><ul><li>A general rule for non-myelinated fibers is the larger the diameter of the fiber, the longer its length constant. </li></ul></ul>
  12. 12. Regenerative Conduction of Action Potentials In Non-Myelinated Fibers: Current Flow <ul><ul><li>Nerve fibers with voltage-sensitive ionic channels are capable of generating action potentials when they are depolarized to threshold either by electrical stimulation or by a generator potential. </li></ul></ul><ul><ul><li>The influx of sodium associated with the action potential provides a source of current, which flows down the longitudinal axis of the nerve fiber in both directions away from the point of stimulation. </li></ul></ul>
  13. 13. Regenerative Conduction of Action Potentials In Non-Myelinated Fibers: Current Flow <ul><ul><li>If enough charge reaches the next &quot;patch&quot; of membrane to depolarize it to threshold, an action potential is initiated at that patch. Because these &quot;patches&quot; of membrane are infinitesimally close to one another, the neighboring patch of membrane always reaches threshold. The influx of sodium at the neighboring patch provides additional charge, which also flows down the longitudinal axis of the nerve, continuing this process of sequential excitation of neighboring patches of membrane. The process whereby action potentials are continuously generated along a nerve fiber is known as regenerative conduction . </li></ul></ul><ul><ul><li>This process accounts for long distance signaling in the nervous system. It is effective up to distances of one meter or more whereas electrotonic conduction is only effective up to approximately five millimeters. </li></ul></ul>
  14. 14. REGENERATIVE CONDUCTION OF ACTION POTENTIALS IN NON-MYELINATED FIBERS: POTENTIAL RECORDINGS <ul><ul><li>The process of regenerative conduction allows the action potential to travel along the entire length of a nerve fiber without any degradation in the size or duration of the signal. </li></ul></ul><ul><ul><li>Unlike electrotonic conduction, which effectively transfers information over very short distances, regenerative conduction provides the capability of long-distance communication. </li></ul></ul>
  15. 15. REGENERATIVE CONDUCTION OF ACTION POTENTIALS IN MYELINATED NERVE FIBERS <ul><ul><li>Some nerve fibers have a very unique structure that has a dramatic effect on their ability to regeneratively conduct action potentials. Schwann cells closely associated with nerve fibers can envelop a section of a nerve fiber. The membrane of the Schwann cell wraps around the nerve fiber many times, providing a region of very high resistance called the myelin sheath . This association takes place along the entire length of the axon. </li></ul></ul><ul><ul><li>The region of the nerve fiber between myelinated areas, where the nerve membrane is exposed to the extracellular space, is termed the Node of Ranvier . The myelinated area of the nerve is referred to as the internodal region . </li></ul></ul><ul><ul><li>Voltage-sensitive ionic channels are only found in the Nodes of Ranvier. They are completely absent from the internodal regions enveloped by myelin sheaths. </li></ul></ul>
  16. 16. SALTATORY CONDUCTION: CONDUCTION IN THE INTERNODE <ul><li>The action potential causes local currents to flow in both directions along the axon. These local currents cause electrotonic spread of the waveform of the action potential through the internode. The magnitude of this waveform is smaller than that of the action potential recorded in the node. </li></ul><ul><li>The maximum amplitude of the action potential in the node and the decreasing maximum electrotonic potential changes take place throughout the internode. </li></ul><ul><li>The internode, where there are no voltage-gated channels, the threshold potential is infinite, while in the Node of Ranvier it is at a potential approximately 10 mV depolarized from the resting potential. </li></ul>
  17. 17. SALTATORY CONDUCTION: CONDUCTION IN THE NODE OF RANVIER <ul><ul><li>In the Node of Ranvier, the threshold is approximately 10 mV greater than the resting potential. For a typical myelinated fiber, the electrotonic decay in the internode reduces the magnitude of the action potential waveform from 100 mV to between 40 and 60 mV. Thus, the electrotonic potential at the next node is 4 to 6 times the threshold for action potential initiation and an action potential will be generated. </li></ul></ul><ul><ul><li>The cycle of “action potential generation ==> electrotonic spread ==> action potential generation” repeats along the entire length of the nerve fiber. This is the fundamental process of AP conduction in myelinated nerve fibers. </li></ul></ul><ul><ul><li>The AP appears to jump from Node of Ranvier to Node of Ranvier because electrotonic conduction within the internodes is much faster than regenerative conduction in the nodes. </li></ul></ul>
  18. 18. EFFECTS OF DEMYELINATION ON THE SPACE CONSTANT <ul><li>Some diseases such as multiple sclerosis are characterized by demyelination of nerve fibers. </li></ul><ul><li>The illustration shows the effects of this demyelination by illustrating what happens to electrotonic conduction along an internode of a myelinated nerve fiber when the myelin sheath along the internode is removed. </li></ul>
  19. 19. EFFECTS OF DEMYELINATION ON THE SPACE CONSTANT <ul><ul><li>Typically, the electrotonically conducted action potential is suprathreshold when it reaches the next distal node. However, demyelination decreases the length constant to the extent that this is no longer true and regenerative conduction fails as the demyelinated fiber does not depolarize to threshold. </li></ul></ul><ul><ul><li>The Schwann cells that create the myelin sheath also serve as receptors for hormones and other chemical substances. In addition to the role they play as structural cells, we are beginning to realize their importance in regulating the function of nerve cells, particularly those in the central nervous system. </li></ul></ul>
  21. 21. CONDUCTION OF INFORMATION ALONG A NERVE FIBER <ul><ul><li>Illustrated is a typical vertebrate spinal motor neuron. Electrotonic conduction of synaptic potentials takes place in the dendrites and soma of the cell. These signals result from the activity of synapses on the dendrites and cell body. The synaptic potentials sum, integrating all the input to this particular cell. Information is carried in the dendrites and cell body in the magnitude of the net electrotonic response. </li></ul></ul>
  22. 22. CONDUCTION OF INFORMATION ALONG A NERVE FIBER <ul><ul><li>Voltage-sensitive sodium and potassium channels are present in the axon hillock and distal regions of the nerve fiber. If the sum of the electrotonic responses (synaptic potentials) conducted to the axon hillock is greater than the threshold potential, an action potential results. The action potential conducts regeneratively in the axonal region of the nerve (by saltatory conduction if the nerve is myelinated). </li></ul></ul>
  23. 23. CONDUCTION OF INFORMATION ALONG A NERVE FIBER <ul><ul><li>Myelination terminates at the distal end of the nerve fiber. In this region there are voltage sensitive calcium channels along with the sodium and potassium voltage-sensitive channels. Action potentials in the nerve terminals cause an influx of Ca due to the opening of L-type calcium channels. The resultant increase in intracellular calcium is important for synaptic transmission. </li></ul></ul>
  24. 24. MIX OF GRADED AND ALL-OR-NONE RESPONSES <ul><ul><li>Illustrated is the mix between graded (electrotonically conducted) signals and all-or-none (regeneratively conducted) signals in a nervous pathway. </li></ul></ul><ul><ul><li>The frequency of action potentials generated at the axon hillock is proportional to the magnitude of the net electrotonic response at that location. </li></ul></ul><ul><ul><li>Information about the sum of the electrical activity reaching the axon hillock is carried in the frequency of these action potentials. </li></ul></ul>
  25. 25. MIX OF GRADED AND ALL-OR-NONE RESPONSES <ul><ul><li>There is a limit to the frequency of action potentials that a nerve fiber can carry. As the frequency of action potentials increases, the time between action potentials decreases. When this time is too short, it impinges on the refractory period of the nerve. The absolute refractory property of the nerve sets the upper limit on the frequency of action potentials it can conduct. </li></ul></ul>
  26. 26. Fiber Types that Compose a Typical Nerve <ul><ul><li>A nerve trunk is composed of the axons of a large number of individual nerve fibers. A large nerve trunk may contain thousands of individual nerve fibers, both myelinated and non-myelinated. </li></ul></ul><ul><ul><li>The table provides the standard classification of fiber types found in a nerve trunk along with the typical functions served by the fibers. </li></ul></ul>
  27. 27. COMPOUND ACTION POTENTIAL: CLINICAL RECORDING <ul><ul><li>The graph is a reproduction of clinical recording of a monophasic compound action potential from a nerve that contains A, B, and C type fibers. The responses from these different fiber types are distributed along the time axis because each of these fiber types has a different conduction velocity. </li></ul></ul><ul><ul><li>As a result, action potentials from fibers with a slower conduction velocity take longer to travel from the stimulating electrode to the first recording electrode. This property can be used to calculate the conduction velocity of the various types of axons within a nerve. </li></ul></ul><ul><ul><li>Conduction velocity information can be used to classify the nerve types contributing to the monophasic compound action potential. </li></ul></ul>
  28. 28. MEASURING CONDUCTION VELOCITY <ul><li>The conduction velocities of the various fiber types comprising a nerve can be calculated from the monophasic compound action potential in the following way: </li></ul><ul><li>Stimulate a nerve trunk under the cathode (C, negative lead) of the voltage stimulator. A stimulus artifact will be detected by the voltmeter at the time of the stimulus. </li></ul><ul><li>Measure the distance (d) between the cathode and the first recording electrode. </li></ul><ul><li>Measure the time (t1, t2, and t3) from the stimulus artifact to each peak of the monophasic action potential. </li></ul>
  29. 29. MEASURING CONDUCTION VELOCITY <ul><ul><li>A conduction velocity of 100 m/sec could only have arisen from a type A fiber. </li></ul></ul><ul><ul><li>Conduction velocities calculated in this way are actually the average conduction velocities of the fibers contributing to a peak. </li></ul></ul><ul><ul><li>Every peak is broad (spread out along the time axis) because not all fibers of a particular type have exactly the same conduction velocity. </li></ul></ul>
  30. 30. TRANSPORT ALONG MICROTUBULES, A CLASS OF CYTOSKELETON PROTEIN <ul><ul><li>The cytoskeleton is a network of filamentous proteins found throughout the cytoplasm of eucaryotic cells. There are three types of cytoskeletal proteins; actin filaments, intermediate filaments, and microtubules. All three are involved in organizing the contents of the cytoplasm and connecting complexes of intracellular proteins and organelles. </li></ul></ul><ul><ul><li>Nervous tissue has particularly high concentrations of microtubules. Besides serving other functions, they provide a highway along which molecules are transported both toward and away from the nucleus of the cell. Therefore, microtubules are involved in the flow of information within the cell. For this reason we will describe the basic properties of particle movement along microtubules. </li></ul></ul>
  31. 31. COMPOSITION OF MICROTUBULE <ul><ul><li>Microtubules are hollow tubes made up of tubulin. There are two globular polypeptides within the cytoplasm called - and -tubulin. These polypeptides will spontaneously assemble in the cytoplasm to form protofilaments composed of alternating - and -tubulin. Thirteen of these protofilaments join in parallel to form a hollow cylinder, which is the microtubule. </li></ul></ul><ul><ul><li>Microtubules are very dynamic structures; they are constantly assembling and disassembling. While the average life of a tubulin molecule is greater than 20 hours, the half-life of a microtubule is approximately 10 minutes . </li></ul></ul>
  32. 32. DISTRIBUTION OF MICROTUBULES WITHIN NERVE CELLS <ul><ul><li>Both the axons and dendrites of nerve fibers have high concentrations of microtubules. One end of each microtubule is anchored in the centrosome, an organelle juxtaposed to the cell nucleus. The rapidly growing end of the filament is referred to as the plus end; it usually is the free end pointing away from the centrosome. The more slowly growing end of the filament is referred to as the minus end; it usually is the end anchored in the centrosome. </li></ul></ul><ul><ul><li>A number of microtubule-associated proteins (MAPs) differentially attach to the microtubules and confer unique properties and functions. </li></ul></ul>
  33. 33. MOTOR PROTEINS <ul><ul><li>Two motor proteins, kinesin and dynein, move substances along microtubules. Both are composed of two heavy chains, which form globular heads, and several smaller light chains. </li></ul></ul><ul><ul><li>The globular heads attach to the microtubules and use the energy from the hydrolysis of ATP to move. </li></ul></ul><ul><ul><li>The transported substances attach to the other end of these molecules. </li></ul></ul>
  34. 34. MOTOR PROTEINS <ul><ul><li>In general, kinesin moves particles away from the centrosome, while dynein moves particles toward the centrosome. Kinesin is very important in supplying the nerve terminals with transmitter-containing vesicles and enzymes necessary for transmitter synthesis. </li></ul></ul><ul><ul><li>Dynein is important in the cellular response to neural injury. Ciliary neurotrophic factor (CNTF) normally is present in high concentrations within the Schwann cells that form the myelin sheath around peripheral motor neurons. </li></ul></ul><ul><ul><li>Peripheral nerve damage releases CNTF from these cells. The CNTF is taken up by the injured motor nerve and transported along the microtubules to the cell body, where it acts to prevent death of the injured cell. </li></ul></ul>
  35. 35. Thank You For Your Attention!