Membrane Dynamics

LECTURE OUTLINE (CHAPTER 5)

LECTURE OBJECTIVES

1. Describe the structure and dynamic nature of the cell membrane
2. Demonstrate how extracellular signals generate intracellular events.
3. Summarize the physical laws and biological processes which govern solute and solvent transport across the cell membrane.
4. Establish how electrochemical gradients are responsible for establishing a membrane potential.

LECTURE OUTLINE

 I. STRUCTURE-FUNCTION OF THE CELL MEMBRANE (See: Pages 53-58)

    A. Cell membrane--the barrier between what goes on in the cytoplasm
       and the cell's immediate environment 
         1. But is it a true "barrier?"   
    B. Overall Structure of Cell Membrane
       1. Most of the cell membrane is composed of phospholipid. The polar 
          ends are lipophobic (=dissolves in lipid with difficulty); the fatty acid tails 
          are lipophilic (=dissolves in lipids easily). 
          a. Proteins imbedded in the lipid bilayer have many different functions.  
                   1) Receptors 
                   2) Ion channels and carrier molecules
                   3) Docking proteins
                   4) Cell-adhesion molecules (CAMs)
                   5) Glycoproteins, glycolipids, etc.
          b. Cholesterol
     C. Cell membrane in cell-cell interactions.
          1. Desmosomes
          2. Tight junctions 
          3. Gap junctions (connexons)
 II.  MEMBRANE TRANSPORT

Cell membrane is selectively permeable (Animations of transport mechanisms) 
     A. SOLVENT FLOW.
          1. Osmosis is movement of water down its own concentration gradient. 
               a. Colligative properties
               b. Tonicity (Animation) 
          2. Filtration - occurs when there is greater hydrostatic 
             pressure on one side of a membrane than on the other
               a. Solvent drag
     B. SOLUTE FLOW--Physical principles governing movement of solutes.
          1. Diffusion (Example: movement of oxygen from lung to blood)
               a. Factors influencing diffusion rate across the cell membrane.
                    1) Concentration gradient
                    2) Membrane permeability (solute)
                    3) Surface area
                    4) Molecular weight of solute
                    5) Membrane thickness
               b. Fick's Law of Diffusion
                    1) Importance of diffusion coefficient (e.g. K+ > Na+)
          2. Facilitated diffusion (e.g., glucose transport from blood into the cells)
               a. Involves a carrier molecule, but solute moves down its conc. gradient
               b. Characteristics of carrier-mediated transport
          3. Active Transport  
               a. Movement of solute against a concentration gradient
               b. Carrier-mediated transport
               c. Energy (ATP) is expended
                     1) Primary Active Transport
                         a) Structural and biochemical characteristics of the 
                            ATPase pump
                         b) Example: Na+/K+ ATPase pump (Animation)
                    2) Secondary Active Transport 
                         a) Co-transport of Na+ and glucose (Animation: Co-transport)
   C. VESICULAR TRANSPORT
         1. Phagocytosis of bacteria, dead cells, etc.
         2. Receptor-mediated endocytosis and exocytosis (Animation: LDL)

III. ELECTROCHEMICAL BASIS FOR THE RESTING POTENTIAL

     A. Movement of ions (=charged particles) is influenced by two factors.
          1. Electrical gradient.
          2. Concentration gradient.
          3. Electrochemical gradients are critical in nerve/muscle impulses
     B.  Membrane potential: - charge inside membrane and + charge outside
     C. Na+, K+, and cytosolic anions are responsible for 
	      membrane potential
          1. Na+, K+, & anion distribution across the resting membrane (Table)
          2. What factors determine this ion distribution?
               a. Na+/K+ pump, but its influence is slight
               b. The K+ and Na+ electrochemical gradients
               c. Equilibrium Potential (E) and the Nernst Equation
                    1) Limitations of Nernst Equation
               d. Goldman equation (=GHK equation) 
          3. Summary: Animation of resting potential **

Reading Assignment. For the next lecture, please read Chapter 6.



STUDY QUESTIONS ON MEMBRANE DYNAMICS (Chapter 5)

    BASIC FACTS AND TERMS

  1. Describe the fluid mosaic model of membrane structure. What are the functions of the major components? Which components do not move easily? Why don't they?

  2. Give at least four different functions for the proteins that are embedded in the cell membrane.

  3. What is Fick's law of diffusion? What factors influence the rate of diffusion across a membrane? Give examples of how membranes might be altered in a biological system to change the rate of diffusion. Can you give a few examples of where diffusion is important for proper physiological function

  4. What are desmosomes, tight junctions, and gap junctions? Under which circumstances is each important?

  5. Compare and contrast the major avenues of water transport across the cell membrane. Give an example of where each is important in human physiology. How are solutes transported across the cell membrane? Compare and contrast the functional characteristics of each transport mechanism. Give an example of how each is important in human physiology.

  6. Define and give the physiological significance (how or why it is important) for the following:

    • Receptor
    • Micelle
    • Secondary active transport
    • Symport
    • Antiport
    • Amplification (of a signal)
    • Connexon
    • Extracellular Fluid (ECF)
    • Intracellular Fluid (ICF)
    • Cyclic AMP
    • Protein kinase
    • Phagocytosis
    • Pinocytosis
    • Receptor-mediated endocytosis
    • Gated channels


    CONCEPTS

  7. There are a number of links to animations in the above lecture outline. A review of these animations will help you understand the dynamics of membrane function.

  8. Which ions (Na+, K+, Cl-, protein-) have a high concentration outside the nerve cell and which have a high concentration inside the nerve cell? What is the direction of the electrical and chemical (=conscentration) gradients for Na+, K+, and Cl-?

  9. Use the Nernst equation to calculate the Equilibrium Potential (E) for K+, and Na+. Use concentrations of K+ and Na+ given in the this Table.

  10. Neurons are only slightly permeable to sodium ions. In which direction is the concentration gradient for sodium? Why? In which direction is the electrical force for sodium? Why?

  11. Does the Na+/K+ ATPase pump move sodium and potassium with or against their respective concentration gradients? What provides the energy to operate the pump? Describe the sequence of events which results in the transport of 3Na+ and 2K+.

  12. Read about vesicular transport in the Silverthorn. What mechanisms exist, how do they work, and how is each important in cellular transport? Look at this Animation for an important example involving low density lipoprotein (LDL) transport.

  13. Read about transepithelial transport in the Silverthorn. What is it and how is it important? Give some examples.

  14. What does the term "resting membrane potential" in a neuron mean? What is a typical value for the resting membrane potential? How important is the Na+/K+ ATPase at determined membrane potential? What specific ion manipulations might alter resting membrane potential?

  15. Review the Nernst and Goldman equations. How are the Nernst equation and Goldman equations applied to understanding membrane potential? Why does the Goldman equation more closely reflect what is actually happening?


    REASONING AND PROBLEM SOLVING

  16. Because of its charge, glucose normally diffuses through the cell membrane very slowly. However, facilitated diffusion of glucose occurs more rapidly as long as the carrier molecules are not saturated. Given Fick's Law of Diffusion, which parameter(s) must change to permit this more rapid diffusion in the presence of a carrier. Explain.

  17. What are the possibilities for how drugs might act at the level of the receptor? In class, I said that a drug could act by competitive inhibition. But some drugs act on the receptor by allosteric (=noncompetitive) inhibition. How might a drug inhibit a receptor in an allosteric manner?

  18. In carrier-mediated transport of Solute Q, there is always the possibility that a similarly-shaped molecule might compete for the transport protein (that is, act as a competitive antagonist to transport of the Solute Q). Graph the rate of Solute Q transport (Y axis) against increasing Solute Q concentration (X axis) in the 1) presence and 2) absence of a set amount of competitive antagonist. Explain. Would you expect to find a similar effect in other systems which employ this "lock and key" interaction (e.g., between a substrate and its enzyme or a neurotransmitter and its receptor)? Explain.

  19. When William was helping victims following a devastating earthquake he developed severe diarrhea. He was diagnosed as having cholera, a disease transmitted through unsanitary water supplies that have been contaminated by fecal material from infected individuals. In this condition, an increase in cAMP (acting as a second messenger) in the intestinal cells opens Cl- channels in the luminal membranes of these cells, thereby increasing the secretion of Cl- from the cells into the intestinal lumen tract. By what mechanisms would Na+ and water be released into the lumen in accompaniment to the Cl- secretion? How does this secretory response account for the severe diarrhea charactersitic of cholera?

  20. Calculate the Equilibrium Potential (E) for Chloride (Cl-) with an extracellular concentration of 110 mM/l and an intracellular concentration of 7mM/l. If the Chloride gates opened in a motor neuron, what would happen to resting potential, if anything? Explain your reasoning. Is Cl- a major player in establishing the resting potential of a motor neuron?

  21. Some references cite that the internal Na+ concentration in a resting motor neuron is about 5 mM, rather than 15 mM. Calculate the effect of lowering [Na+]i to 5 mM. Does this difference have a major effect on resting membrane potential (Vr)? Remember that given the values listed in this Table, the calculated Vr is actually -71.1 mV, not -70 mV. What additional factors might explain this discrepency of 1.1 mV?

  22. Although only muscle and nerve cells generate an electrical inpulse, is it likely that non-neural/muscular cells (e.g., epithelial cells) have a charge across the cell membrane? Defend your position.

  23. If you raised the external K+ concentration 10 fold (see Table for normal values), what change would occur in the nerve resting potential? (Use the Goldman equation to calculate the effect.) What effect would this change have on the ability of the nerve to fire? External K+ concentration in the brain is carefully regulated by a special group of cells, called astrocytes. Why is regulation of K+ especially important for normal brain function?
 



Last revised: January 24, 2008