Figure

Human Anatomy & Physiology Premium Course

Human Anatomy and Physiology Study Course

Get Instant Access

The increase in intracellular concentration as a substance diffuses from a constant extracellular concentration until diffusion equilibrium (Q = C0) is reached across the plasma membrane of a cell.

The magnitude of the net flux is directly proportional to the difference in concentration across the membrane (Co — C), the surface area of the membrane A, and the membrane permeability constant kp:

The numerical value of the permeability constant kp is an experimentally determined number for a particular type of molecule at a given temperature, and it reflects the ease with which the molecule is able to move through a given membrane. In other words, the greater the permeability constant, the larger the net flux across the membrane for any given concentration difference and membrane surface area.

The rates at which molecules diffuse across membranes, as measured by their permeability constants, are a thousand to a million times smaller than the diffusion rates of the same molecules through a water layer of equal thickness. In other words, a membrane acts as a barrier that considerably slows the diffusion of molecules across its surface. The major factor limiting diffusion across a membrane is its lipid bilayer.

Diffusion through the Lipid Bilayer When the permeability constants of different organic molecules are examined in relation to their molecular structures, a correlation emerges. Whereas most polar molecules diffuse into cells very slowly or not at all, nonpolar molecules diffuse much more rapidly across plasma membranes—that is, they have large permeability constants. The reason is that nonpolar molecules can dissolve in the nonpolar regions of the membrane—regions occupied by the fatty acid chains of the membrane phospholipids. In contrast, polar molecules have a much lower solubility in the membrane lipids. Increasing the lipid solubility of a substance (decreasing the number of polar or ionized groups it contains) will increase the number of molecules dissolved in the membrane lipids and thus increase its flux across the membrane. Oxygen, carbon dioxide, fatty acids, and steroid hormones are examples of nonpolar molecules that diffuse rapidly through the lipid portions of membranes. Most of the organic molecules that make up the intermediate stages of the various metabolic pathways (Chapter 4) are ionized or polar molecules, often containing an ionized phosphate group, and thus have a low solubility in the lipid bilayer. Most of these substances are retained within cells and organelles because they cannot diffuse across the lipid barrier of membranes.

Diffusion of Ions through Protein Channels Ions such as Na+, K+, Cl—, and Ca2+ diffuse across plasma membranes at rates that are much faster than would be predicted from their very low solubility in membrane lipids. Moreover, different cells have quite different permeabilities to these ions, whereas nonpolar substances have similar permeabilities when different cells are compared. The fact that artificial lipid bilay-ers containing no protein are practically impermeable to these ions indicates that it is the protein component of the membrane that is responsible for these permeability differences.

As we have seen (Chapter 3), integral membrane proteins can span the lipid bilayer. Some of these proteins form channels through which ions can diffuse across the membrane. A single protein may have a conformation similar to that of a doughnut, with the hole in the middle providing the channel for ion movement. More often, several proteins aggregate, each forming a subunit of the walls of a channel (Figure 6-5). The diameters of protein channels are very small, only slightly larger than those of the ions that pass through them. The small size of the channels prevents larger, polar, organic molecules from entering the channel.

Ion channels show a selectivity for the type of ion that can pass through them. This selectivity is based partially on the channel diameter and partially on the charged and polar surfaces of the protein subunits that form the channel walls and electrically attract or repel the ions. For example, some channels (K channels) allow only potassium ions to pass, others are specific for sodium (Na channels), and still others allow both sodium and potassium ions to pass (Na,K channels). For this reason, two membranes that have the same permeability to potassium because they have the same number of K channels may have quite different permeabilities to sodium because they contain different numbers of Na channels.

Vander et al.: Human I I. Basic Cell Functions I 6. Movement of Molecules I I © The McGraw-Hill

Physiology: The Across Cell Membranes Companies, 2001

Mechanism of Body Function, Eighth Edition

Vander et al.: Human I I. Basic Cell Functions I 6. Movement of Molecules I I © The McGraw-Hill

Physiology: The Across Cell Membranes Companies, 2001

Mechanism of Body Function, Eighth Edition

Channel Subunit

FIGURE 6-5

Model of an ion channel composed of five polypeptide subunits. (a) A channel subunit consisting of an integral membrane protein containing four transmembrane segments (1, 2, 3, and 4), each of which has an alpha helical configuration within the membrane. Although this model has only four transmembrane segments, some channel proteins have as many as 12. (b) The same subunit as in (a) shown in three dimensions within the membrane with the four transmembrane helices aggregated together. (c) The ion channel consists of five of the subunits illustrated in b, which form the sides of the channel. As shown in cross section, the helical transmembrane segment (a,2) (light purple) of each subunit forms the sides of the channel opening. The presence of ionized amino acid side chains along this region determines the selectivity of the channel to ions. Although this model shows the five subunits as being identical, many ion channels are formed from the aggregation of several different types of subunit polypeptides.

FIGURE 6-5

Model of an ion channel composed of five polypeptide subunits. (a) A channel subunit consisting of an integral membrane protein containing four transmembrane segments (1, 2, 3, and 4), each of which has an alpha helical configuration within the membrane. Although this model has only four transmembrane segments, some channel proteins have as many as 12. (b) The same subunit as in (a) shown in three dimensions within the membrane with the four transmembrane helices aggregated together. (c) The ion channel consists of five of the subunits illustrated in b, which form the sides of the channel. As shown in cross section, the helical transmembrane segment (a,2) (light purple) of each subunit forms the sides of the channel opening. The presence of ionized amino acid side chains along this region determines the selectivity of the channel to ions. Although this model shows the five subunits as being identical, many ion channels are formed from the aggregation of several different types of subunit polypeptides.

Vander et al.: Human Physiology: The Mechanism of Body Function, Eighth Edition

Movement of Molecules Across Cell Membranes CHAPTER SIX

Role of Electric Forces on Ion Movement Thus far we have described the direction and magnitude of solute diffusion across a membrane in terms of the solute's concentration difference across the membrane, its solubility in the membrane lipids, the presence of membrane ion channels, and the area of the membrane. When describing the diffusion of ions, since they are charged, one additional factor must be considered: the presence of electric forces acting upon the ions.

There exists a separation of electric charge across plasma membranes, known as a membrane potential (Figure 6-6), the origin of which will be described in Chapter 8. The membrane potential provides an electric force that influences the movement of ions across the membrane. Electric charges of the same sign, both positive or both negative, repel each other, while opposite charges attract. For example, if the inside of a cell has a net negative charge with respect to the outside, as it does in most cells, there will be an electric force attracting positive ions into the cell and repelling negative ions. Even if there were no difference in ion concentration across the membrane, there would still be a net movement of positive ions into and negative ions out of the cell because of the membrane potential. Thus, the direction and magnitude of ion fluxes across membranes depend on both the concentration difference and the electrical difference (the membrane potential). These two driving forces are collectively known as the electrochemical gradient, also termed the electrochemical difference across a membrane.

It is important to recognize that the two forces that make up the electrochemical gradient may oppose

Seperation Cells From Plasma

FIGURE 6-6

The separation of electric charge across a plasma membrane (the membrane potential) provides the electric force that drives positive ions into a cell and negative ions out.

FIGURE 6-6

The separation of electric charge across a plasma membrane (the membrane potential) provides the electric force that drives positive ions into a cell and negative ions out.

each other. Thus, the membrane potential may be driving potassium ions, for example, in one direction across the membrane, while the concentration difference for potassium is driving these ions in the opposite direction. The net movement of potassium in this case would be determined by the magnitudes of the two opposing forces—that is, by the electrochemical gradient across the membrane.

Regulation of Diffusion through Ion Channels Ion channels can exist in an open or closed state (Figure 6-7), and changes in a membrane's permeability to ions can occur rapidly as a result of the opening or closing of these channels. The process of opening and closing ion channels is known as channel gating, like the opening and closing of a gate in a fence. A single ion channel may open and close many times each second, suggesting that the channel protein fluctuates between two (or more) conformations. Over an extended period of time, at any given electrochemical gradient, the total number of ions that pass through a channel depends on how frequently the channel opens and how long it stays open.

In the 1980s, a technique was developed to allow investigators to monitor the properties of single ion channels. The technique, known as patch clamping, involves placing the tip of a glass pipette on a small region of a cell's surface and applying a slight suction so that the membrane patch becomes sealed to the edges of the pipette and remains attached when the pipette is withdrawn. Since ions carry an electric charge, the flow of ions through an ion channel in the membrane patch produces an electric current that can be monitored. Investigators found that the current flow was intermittent, corresponding to the opening and closing of the ion channel, and that the current magnitude was a measure of the channel permeability. By adding possible inhibitors or stimulants to the solution in the pipette (or to the bath fluid, which is now in contact with the intracellular surface of the membrane patch), one can analyze the effects of these agents in modifying the frequency and duration of channel opening. Patch clamping thus allows investigators to follow the behavior of a single channel over time.

Three factors can alter the channel protein conformations, producing changes in the opening frequency or duration: (1) As described in Chapter 7, the binding of specific molecules to channel proteins may directly or indirectly produce either an allosteric or covalent change in the shape of the channel protein; such channels are termed ligand-sensitive channels, and the ligands that influence them are often chemical messengers. (2) Changes in the membrane potential can cause movement of the charged regions on a channel protein, altering its shape—voltage-gated channels

Vander et al.: Human Physiology: The Mechanism of Body Function, Eighth Edition

PART ONE Basic Cell Functions

Intracellular fluid

Lipid bilayer

Open ion channel

Closed ion channel

Extracellular fluid

Was this article helpful?

0 0
Essentials of Human Physiology

Essentials of Human Physiology

This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.

Get My Free Ebook


Responses

  • Lobelia
    Is electrochemical gradient the driving force for ion movement through open gated channels?
    8 years ago

Post a comment