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NERVE PHYSIOLOGY

 

TABLE OF CONTENTS

Updated: Jan. 24, 2008

LECTURE INFORMATION

KEY CONCEPTS IN THIS LECTURE

1. The nerve impulse, or action potential, is a brief (lasting 150 msec) reversal of charge across the nerve membrane. Initially, a slight depolarization of the membrane occurs (i.e., the potential moves from the resting potential of -70 mv towards 0 mv). If the threshold is reached (about -60 mV), depolarization becomes irreversible ("all or none") and a positive spike occurs (+40 mV; this is the charge reversal across the membrane characteristic of action potentials). The spike then hyperpolarizes to -75 mv, and over the next 150 msec the resting potential is re-established.

2. An action potential results from the selective movement of two ions across the plasma membrane of the nerve. The action potential starts with an influx of Na+ through a special channels in the membrane. As a result, there is eventually a + charge inside the membrane (upward swing of spike). This + charge, however, is short-lived because K+ efflux occurs through specific K+ channels and results in renewed hyperpolarization of the membrane (downward swing of spike). Although the net charge outside the membrane is again +, the ion distribution differs from the initial state (i.e., K+ is now outside; Na+ inside). A 3:2 Na+/K+ active transport pump in the plasma membrane helps return the ions to their original distribution (Na+ outside, K+ inside). Operation of this pump requires energy (=ATP).

3. Upon initiation of an "all-or-none" action potential (AP) at the hillock of the axon, the impulse passes along the entire length of the axon at full strength. In motor neurons, the impulse moves quickly because it "leap frogs" from node of Ranvier to node of Ranvier. Upon arrival at the nerve terminal the AP stimulates Ca++ influx which promotes exocytosis of synaptic vesicles and release of neurotransmitter.

4. Information passes between two neurons (or a neuron and a muscle cell) via a synapse. There are two types of synapse, electrical (less common) and chemical. The latter secretes a neurotransmitter which alters the membrane potential of the post-synaptic cell. A synapse can be excitatory (generatingan excitatory post-synaptic potential, EPSP) or inhibitory (inhibitory post-synaptic potential, IPSP). Integration of EPSP's and IPSP's determines the probability that the post-synaptic cell will fire.

LECTURE OUTLINE

I. CHANGES IN MEMBRANE POTENTIAL

  A. Graded Potentials *
     1. Hyperpolarizing stimulus (Neuron less likely to fire) verses
        depolarizing stimulus (Neuron more likely to fire)
     2. Stimulus strength determines extent of response
     3. There is no refractory period so summation is possible.
     4. Passive current spread
          a. Passive current (cable properties) deteriorates with distance because of 
             membrane resistance

  B. Action Potential (=Nerve impulse)
     1. Characteristics of the Action Potential (AP)
          a. At threshold firing is an all-or-none response
          b. Positive feedback accelerates Na+ influx and depolarization
          c. K+ gates open slightly later; the Na+ gates close
     2. AP has a refractory period; no summation occurs

II. ELECTRICAL CHARACTERISTICS OF THE ACTION POTENTIAL

  A. Selective Na+ conductance followed by K+ conductance (See Text CD or 
      this animation).
     1. Importance of positive feedback for Na+
     2. Voltage change affects ion gating *
     3. Na+/K+ ATPase pump re-establishs the Na+ & K+ gradients 
        following repeated firing (Animation of Na+/K+ pump)

  B. Refractory Period
     1. Significance of the refractory period *

  C. Movement of the AP along the axon
     1. neuron structure (dendrite, cell body, hillock, axon, synapse)
     2. Why does the AP start at the trigger zone?

  D. Saltatory conduction: AP jumps from node to node of Ranvier
     1. The myelin sheath (Schwann cell) is separated by nodes of Ranvier
     2. Passive current spread generates an action potential
        at the next node (animation). *

III. SYNAPSES ***

  A. Electrical Synapse
     1. Structure of the gap junction
     2. Electrical properties
          a. fast, less plasticity, usually bidirectional

  B. Chemical Synapse: Acetylcholine as an example
     1. General structure of the chemical synapse
     2. Neurotransmitter release occurs by exocytosis (See Text CD)
     3. Mechanism of neurotransmitter loading and release
          a. transporting vesicles to bouton
          b. loading synaptic vesicles
          c. docking and exocytosis of vesicles (AP & Ca++)-omega body
          d. recycling membrane to form new synaptic vesicles
          e. fates of neurotransmitter (degradation, reuptake, recycling, diffusion)

  C. Neurotransmitter Action
     1. Specific changes on the post-synaptic membrane
     2. Post-synaptic neurotransmitter effects (Animations of signal transduction)
          a. Nicotinic Ach receptor (nAchR) stimulates skeletal muscle (ionotropic)
               1) Action: opens a Na+ - K+ channel on the post-synaptic membrane
          b. Muscarinic Ach receptor (mAchR) inhibits heart muscle (metabotropic)
               1) Action: acts through inhibitory G protein to open K+ channels
          c.  Norepinephrine stimulates heart muscle (metabotropic)
          d. Signal transduction is specific to the target cell ***

IV. INTEGRATION OF POSTSYNAPTIC POTENTIALS  (EPSP/IPSP)

  A. Excititory and inhibitory synapses (Animation)

  B. How integration of multiple inputs is achieved 
     1. Postsynaptic responses
          a. Cell body integrates dendritic inputs
          b. Spatial and temporal summation
          c. Cancellation of a EPSP by a IPSP ***
     2. Presynaptic inhibition and facilitation

  C. Convergence and divergence in neuronal pathways
  
  D. Summary of communication between neurons (Carlson animation)

STUDY QUESTIONS

  1. Compare and contrast the functional characteristics of a graded response (e.g., post-synaptic potential) and an all-or-none response (e.g., actionpotential)

  2. Contrast the functional charactersitics of an electrical synapseand a chemical synapse.

  3. Describe the permeability changes and ionic fluxes which occur during the action potential (AP). What factors affect the timing of ion conductance during the AP?

  4. Outline the process of neurotransmitter release into a synapse. Start with thearriving action potential and end with neurotransmitter release.

  5. If you electricially stimulated the middle of an axon to elicit anaction potential, would the action potential travel in one or bothdirections from the point of stimulation? Explain why? How far along the axon would the action potential go? Why? See this Animation for answer.

  6. What happens to resting membrane potential if you lower the the concentration of K+ on the inside of the cell from 150 mM to 135 mM?

  7. What is passive current flow along the length of the neuron and how it is important to neuronal function?

  8. Curare (=dart gun poison from Africa) is a drug that causes paralysis of skeletal muscle. The drug acts at the synapse between the nerve and the muscle cell. Acetylcholine is the neurotransmitter at this synapse. First, what are some of the ways curare might act at the neuromuscular junction to cause paralysis? Second, pick one of these possibilities and describe how you might test if it acts in this manner.

  9. When a neurotransmitter is said to be "excitatory", what does that mean with regard to: 1) the post-synaptic potential, 2) ion flux at the post-synaptic membrane, and 3) the probability that the post-synaptic neuron will fire.

  10. EDTA is a chemical which tightly binds Ca++. When a pre-synaptic nerve isstimulated in the presence of EDTA, it fires an action potential, but transmission of the action potential to the post-synaptic neuron neveroccurs. If you remove the EDTA, the post-synaptic nerve then fires. Given your knowledge of how Ca++ is involved in communciation between neurons, how would you explain these results?How are synaptic vesicles transported to the bouton, and how are they loaded with neurotransmitter?

  11. What are the possible fates of neurotransmitter released into the synaptic cleft?

  12. Contrast 1) temporal and 2) spatial summation of a post-synaptic potential (PSP). Click here

  13. How does a neurotransmitter act at the membrane of a post-synaptic neuron?

  14. What is an EPSP and an IPSP? What effect does each have on the probability that post-synaptic neuron will fire? How are graded potentials involved in this process?

  15. Distinguish between presynaptic inhibition (see Figure 2.38) and an inhibitory post-synaptic potential (IPSP).

  16. The only thing that we said about Cl- is that this ion is in high concentration in the ECF around the neuron. But there are Cl- gates in the plasma membrane. Can you think of a mechanism by which Cl- would hyperpolarize membrane potential? Explain you answer. So, in general, what do you have to do hyperpolarize a membrane potential?

  17. The diagnosis of a recently discovered medical condition is that serotonin secretion in a particular brain pathway is very low (=the serotonergic neurons are releasing insufficient amounts of the neurotransmitter, serotonin). The NIH asks you to develop a line of research aimed at alleviating this condition. Given your knowledge of how neurotransmitters work, outline a series (more than one) of approaches which you might use to treat this problem. Be usre to use correct physiological terminology.

  18. Define and give the physiological significance (how or why it is neurophysiologically important) for the following terms:
    • resting membrane potential
    • graded pontential
    • all-or-none law
    • hyperpolarization
    • saltatory conduction
    • Schwann cell
    • IPSP and EPSP
    • trigger zone of axon (=hillock)
    • refractory period
    • voltage-gated ion channel
    • passive current loss (along membrane)

  19. Here is a general question on secretion of neurotransmitter. In an outline or a diagram, trace the course of 1) synaptic vesicle formation, 2) vesicle transport to the bouton, 3) vesicle loading with neurotransmitter, and finally 4) vesicle secretion at the synapse. List the specific protein involved at each step and explain how each functions.

  20. Using the following diagram of an action potential, describe what is happening with regard to Na+ flux, K+ flux, and the ATPase pump at each of the letters. When are the Na+ gates open and when are they closed? K+ gates?

  21. One of the simpliest behaviors is a reflex, such as withdrawing you hand when you touch a hot object (See Figure 2-13 in Carlson). Such reflexes are found in most animals and can explain some types of animal behavior. Outline an experimental plan which would identify and characterize the specific neurons involved in this simple reflex (e.g., how many neurons are involved; what are their neurotransmitters, etc.). Refer to Chapter 5 in the text. You will learn more about these techniques in about a week.

ADDITIONAL INFORMATION ON THE INTERNET

Multiple Sclerosis. A good description of this autoimmune disease that attacks myelin--from Harvard University

Communication between nerves. A good animation showing hownerves communicate information in the brain and how cocaine disruptsthis communication.

Action Potential Simulator. A simulator where you can manipulate ion concentrations and determine their effects on the action potential.

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