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Physiology I
Section 1
Transport across cell membranes

Suggested reading:
    Guyton chapters 2 & 4

Key Words

Simple diffusion: Molecular kinetic movement of molecules or ions occurs through a membrane opening or through intermolecular spaces without the necessity of binding with carrier proteins in the membrane. The rate of diffusion is determined by the amount of substance available, by the velocity of kinetic motion, and by the number of openings in the cell membrane through which the molecules or ions can move. Simple diffusion can occur through the cell membrane by two pathways: (1) through the interstices of the lipid bilayer, especially if the diffusing substance is lipid-soluble, and (2) through watery channels in some of the transport proteins. Guyton, page 44

Movement of solutes from an area of high concentration to an area of low concentration. Class notes 7/8/99

Facilitated diffusion: Requires the interaction of a carrier protein with the molecules or ions. The carrier protein aids passage of the molecules or ions through the membrane, probably by binding chemically with them and shuttling them through the membrane in this form. Guyton, page 44

Osmosis: The process of net movement of water caused by a concentration difference of water. Guyton, page 49

Osmotic pressure: The amount of pressure required exactly to stop osmosis. Guyton, page 50

Membrane permeability: How well particles can travel through the membrane are affected by different factors:

1. Thickness of the membrane—The greater the thickness, the less the rate of diffusion.

2. Lipid solubility—The greater the solubility of the substance in the cell membrane lipids, the greater the quantity of substances that dissolves in the membrane and, therefore, that can pass through.

3. Number of protein channels through which the substance can pass—The rate of diffusion is directly related to the number of channels per unit area.

4. The temperature—The greater the temperature, the greater is the thermal motion of molecules and ions in a solution, so that diffusion increases directly in proportion to temperature.

5. The molecular weight of the diffusing substance—this has a complex effect; the velocity of thermal motion of a dissolved substance is inversely proportional to the square root of its molecular weight. Also, as the molecular diameter approaches the diameter of a channel, the resistance increases tremendously, so that a membrane is frequently hundreds to millions of times a permeable to very small molecules as to very large one. Guyton, page 48

Concentration gradient: The rate at which the substance diffuses inward is proportional to the concentration of molecules on the outside because this concentration determines how many molecules strike the outside of the channels each second. On the other hand, the rate at which molecules diffuse outward is proportional to their concentration inside the membrane. Therefore, the rate of net diffusion into the cell is proportional to the concentration on the outside minus the concentration on the inside. Guyton, page 48-49

Electrochemical equilibrium:  Point within a system where the electrical and concentration gradients are such so there is no net movement of particles.  (This definition is not as clear as Dr. Spirito presented it)  Class note 7/15/1999

Osmolality: Osmoles per kilogram of water. The number of particles of a substance that is dissolved in water. The amount of osmotic pressure exerted by a solute is proportional to the concentration of the solute in numbers of molecules or ions. The unit "osmole" is used in place of grams. Guyton, page 50-51

Osmolarity: Osmolar concentration expressed as osmoles per liter of solution rather than osmoles per kilogram of water. Although, strictly speaking, it is osmoles per kilogram of water (osmolality) that determines the osmotic pressure, nevertheless, for dilute solutions, such as those in the body, the quantitative differences between osmolarity and osmolality are less than 1 per cent. Because it is far more practical to measure osmolarity than osmolality, this is the usual practice in almost all physiological studies. Guyton, page 51

Oncotic pressure (colloid osmotic pressure): See Guyton page 190.
Osmotic pressure related to large proteins that are trapped in the vessels. Water wants to come in r/t many proteins in the vessels (concentration gradient).
Class notes 7/8/99

Tonicity:  Comparative measure.  Compares osmotic force of one fluid to a reference solution.  If reference solution is not named, it can be assumed it is plasma.  Class notes 7/13/99

Active transport: When a cell membrane moves molecules or ions uphill against a concentration gradient (or uphill against an electrical or pressure gradient). Guyton, page 51 There are 2 types of active transport:

1. Primary active transport—The energy is derived directly from the breakdown of adenosine triphosphate (ATP) or some other high energy phosphate compound. (Sodium-Potassium pump, Calcium pump, Hydrogen ions)

2. Secondary active transport (Co-transport or Counter-transport)—The energy is derived secondarily from energy that has been stored in the form of ionic concentration differences between the two sides of a membrane, created in the first place by primary active transport. (Glucose and Amino acids, sodium counter transport of calcium and hydrogen ions)

 

Learning Objectives

Name and discuss four factors affecting the rate of diffusion of a substance—  

  1. Membrane permeability – all the factors listed in the membrane permeability answer will apply here as well.
  2. Concentration - the rate at which the substance diffuses inward is proportional to the concentration of molecules on the outside. The rate of diffusion outward is proportional to their concentration inside the membrane.
  3. Electrical potential of the ions – if an electrical potential is applied across the membrane, because of their electrical charges, ions will move through the membrane even though no concentration difference exists to cause their movement. Reference is made to the Nernst equation, which will be discussed in the next section.
  4. Pressure difference – There can be pressure differences btw the sides of the membrane. I.e. Capillary pres is 20mmHg inside. The pressure actually means the sum of all the forces of the different molecules hitting the surface area at a given instant. So if the pres. is higher on one side than the other, it is actually the sum of all the forces of the molecules moving and hitting the sides. Usually this means there are more molecules on the side with the higher pressure. The result of this increased movement is that more energy is available to cause net movement of molecules from the high pressure side to the low pressure side. (Guyton p48-9)

Name and describe at least two different routes by which biologically important molecules diffuse through cell membranes—  

  1. Lipid bilayer - lipid soluble substances can diffuse through as if the membrane didn’t exist such as the resp. gases. Lipid solubility plays a role however in that the higher the solubility the greater the movement of these substances.
  2. Protein channels – watery pathways through the interstices of the protein molecule. They are usually selectively permeable to certain substances and many of the channels can be opened or closed by gates. Movement also will depend on the size of the molecule trying to diffuse through and the size of the gate. This also will pertain to its shape and the nature of the electrical charges. Chemical gating is when the protein binds with the molecule and causes a conformational change in the protein molecule, which will open or close the gate.
  3. Water filled pores – There are very few and they can only move one substance through at a time. They are also very small and wouldn’t move the lipid soluble substances. (Guyton, p 45-6)(Class notes 7/8/99)

Compare and contrast simple diffusion and facilitated diffusion—  Simple diffusion occurs through the protein channels with gates, the water pores and through the lipid bilayer without the use of any interaction with other substances. In facilitated diffusion the must be some interaction with a carrier protein and the molecules trying to move. The carrier protein will bind chemically, its tertiary structure undergoes a change and the new protein moves through the membrane. The concentration changes inside the cell usually cause the protein molecule to release the substrate and will then diffuse back through the membrane alone leaving the substrate behind.

Define "membrane permeability" and list three factors that affect the permeability of cell membranes—How well particles can travel through the membrane are affected by different factors:

1. Thickness of the membrane—The greater the thickness, the less the rate of diffusion.

2. Lipid solubility—The greater the solubility of the substance in the cell membrane lipids, the greater the quantity of substances that dissolves in the membrane and, therefore, that can pass through.

3. Number of protein channels through which the substance can pass—The rate of diffusion is directly related to the number of channels per unit area.

4. The temperature—The greater the temperature, the greater is the thermal motion of molecules and ions in a solution, so that diffusion increases directly in proportion to temperature.

5. The molecular weight of the diffusing substance—this has a complex effect; the velocity of thermal motion of a dissolved substance is inversely proportional to the square root of its molecular weight. Also, as the molecular diameter approaches the diameter of a channel, the resistance increases tremendously, so that a membrane is frequently hundreds to millions of times a permeable to very small molecules as to very large one. Guyton, page 48

Discuss the concept of net movement of a substance across the membrane, and identify the effects of concentration gradients, electrical potential, and pressure on net movement—It is important to remember that substances that can diffuse in one direction can also diffuse in the opposite direction.  Therefore, what is usually important is the net rate of diffusion of a substance in the desired direction.  For example...4 sodium ions may move to the LEFT and 1 sodium ion may move to the RIGHT...so the net movement is 3 sodium ions to the LEFT.  Guyton, page 48

Effects of concentration gradients--The rate at which the substance diffuses inward is proportional to the concentration of molecules on the outside because this concentration determines how many molecules strike the outside of the channels each second.  The higher the concentration gradient...the higher the diffusion rate.  Guyton, page 48-49

Effects of electrical potentials--if an electrical potential is applied across the membrane, because of their electrical charges, ions will move through he membrane even though no concentration difference exists to cause their movement.  A positive charge attracts the negative ions, whereas the negative charge repels them.  Guyton, page 49

Effects of pressure--A higher pressure on one side of a membrane compared to another creates a system where increased amounts of energy are available to cause net movement of molecules from the high pressure side toward the low pressure side.  Guyton, page 49

Identify osmosis, osmotic pressure and its determinants, osmolality, and osmolarity—Osmosis is the net movement of water caused by a concentration difference of water. Guyton, page 49 (water flows down it's concentration gradient, from higher concentration, such as 100% or "pure water", to lower concentration).  Osmotic pressure is the amount of pressure required to exactly stop osmosis… "…the factor that determines the osmotic pressure of a solution is the concentration of the solution in terms of numbers of particles (which is the same as its' molar concentration if it is a not dissociated molecule) and not in terms mass of the solute." (i.e., glucose does not dissociate in solution, & therefore 1 gm molecular weight ,180 gm, has 1 osmole of force. NaCl does dissociate into Na & Cl, therefore 1 gm molecular weight , 58.5 gm, becomes two osmoles of force.) Guyton, page 50

Osmolality is the osmotic pressure in terms of osmoles per kilogram of water. Osmolarity is the osmotic pressure expressed as osmoles per liter of solution. The difference between the two measures is <1%, and Osmolarity is easier to measure. Guyton, page 51 (Osmolarity is how we quantify the tonicity (in other words: putting a number to the force of osmotic pressure) of fluids in body systems. Tonicity being a description of the relationship between one solution (IV fluid) and another liquid (plasma): isotonic, hypertonic, hypotonic.)

Discuss the characteristics of active membrane transport, specifically the membrane Na+ / K+ ATPase, or "sodium pump", and describe its significance in the regulation of cell volume—The characteristics of Active Membrane Transport include: All types of active transport include a carrier protein, a substance to be transported against an energy gradient, and some form of energy.  Active transport involves the expenditure of energy to transport substances.

The type of energy used and the involvement of a secondary substance are variables that define the subtype of active membrane transport. (see definitions of Primary & Secondary Active Transport). Co-transport moves two substances in the same direction, for instance Na flowing down it's concentration gradient into the cell and glucose tagging along for the free ride (a carrier protein holds them together; glucose is traveling against it's concentration gradient). Counter transport moves two substances in oppose directions. The Na K ATPase pump is an Primary Active Transport system Guyton, page 51 that uses counter transport as a mechanism. An example of a Co-transport with Secondary Active Transport would be sodium moving amino acids and glucose against their concentration gradients.  Guyton, page 53

The Na K ATP pump is a complex of two separate globular proteins…although the function of the smaller is not known, it may be an anchor protein…the larger protein (which extends through the bilayer of the cell membrane) has 3 specific features: 1- three sodium receptor sites on the part that protrudes into the cell, 2- two potassium receptor sites on the part that extends out of the cell, 3- near or adjacent to the sodium binding sites ATPase activity. When all receptor sites are filled, the protein configuration changes, reversing the position of the ions relative to the cell. ATP energy is released to push the ions against their concentration gradients. There is a continual net loss of ions (3 out, 2 in), and water follows the sodium out. This method of volume control is important and keeps the cell from swelling & rupture. Swelling cells actually activates the NaK pump.

 

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Last updated 08/20/00 11:06:13 PM