The transport of ions and molecules across epithelia is not only important physiologically, but also provides us with a good opportunity to study the operation of several of the transporters summarized on the "Review of Membrane Transport Page". On the present page, we are going to be looking at two examples from the epithelium of the small intestine, both of which are quite important physiologically and in disorders. Also, closely related processes are at work in other organs.
In simple epithelial, the transporters and ion channels present on the two sides of the cell are different. As the membrane proteins are synthesized, they wind up in two different vesicles, with one type moving to and fusing with the apical membrane, while the other type moves to and fuses with the basolateral membrane.
Adjacent cells of an epithelium, in general, are joined at their edges by tight junctions, which seals the gap between the adjacent cells. Thus, most substances must move through the cells rather than between the cells. As a result, membrane transporters and ion channels in the membranes of the cells are in a position to regulate the movement of substances across the epithelium.
The figure below shows and compares our two examples. Use this for reference as each example is discussed.
On the left in the figure above, notice that glucose in the lumen of the small intestine is transferred across the apical membrane via a co-transporter that also requires that Na+ bind to the transporter. This is significant because both the concentration gradient for glucose and the concentration gradient for Na+ must be taken into account when considering the energetics for the operation of this membrane transporter. To be more specific, the free energy inherent in the concentration gradient for glucose must be added to the free energy for the Na+ concentration gradient to get the overall free energy that drives the operation of the transporter.
Na+ concentration gradient driving glucose transport: Let's take an example. Suppose we are at the very end of the absorption phase of a meal and the concentration of glucose in the lumen in now fairly low. In fact, let us suppose the concentration inside the intestinal cell is higher than in the lumen. An ordinary, facilitated diffusion transporter would move glucose from the cell into the lumen. But since here the transporter is the Na+/glucose transporter, this would not actually happen. Because we can assume a modest concentration of Na+ in the lumen due to intestinal secretions and the food, there would be a strong Na+ concentration gradient tending to move Na+ into the cell,. This is because here, as in all cells, the concentration of Na+ is kept low inside the cell by the ubiquitous Na+/K+ active transporter. Thus the free energy available from the Na+ gradient should be sufficient to move glucose up its concentration gradient, from the lumen into the cell. Notice that ATP energy is not directly required for the transporters moving glucose. It is the energy in the Na+ concentration gradient that drives the "uphill" transport of glucose. This type of energetic coupling illustrates the importance of cotransporters.
Once the glucose is concentrated in the intestinal epithelial cell to a level higher than in the extracellular fluid, then an ordinary facilitated diffusion carrier moves glucose from the cell into the extracellular fluid and hence the blood.
Glucose concentration gradient driving Na+ transport: A second example involving the Na+/glucose transporter is provided by oral rehydration solutions. In a seriously dehydrated person, drinking water alone does not solve the problem. The water by itself simply dilutes the extracellular fluid, which can be a problem. Also, under these conditions the extra water likely is soon lost in the urine. To expand the extracellular fluid volume, which is what is required, Na+ must be added to the extracellular fluid. This is because Na+ is the most numerous ion in the extracellular fluid. As more Na+ is added to the extracellular fluid, more water is retained to increase the extracellular fluid volume. Thus, Na+ is usually the most important substance in the oral rehydration fluid.
If you read the label of an oral rehydration solution, you will see that there is also substantial glucose in the solution. The extra energy is likely helpful. But the main reason is the abundant Na+/glucose cotransporter. Glucose must be present in the lumen for this transporter to move Na+ from the lumen. But notice also that with abundant glucose in the lumen, the concentration of glucose in the lumen is now higher than glucose in the extracellular fluid. Thus, the free energy in the glucose concentration is added to that from the Na+ concentration gradient for the operation of the Na+/glucose transporter. This potentially increases the rate of Na+ transport from the lumen into the body.
The secretion of fluid into the lumen of the intestines plays a role in normal physiology. But also, of course, can be quite prominent in some infections. The increased secretion of fluid and resulting diarrhea can be helpful in flushing out pathogens. But, of course, dehydration can become a serious issue. And also the pathogen is spread more quickly and widely.
Refer in the figure above to the diagram on the right. Fluid secretion is driven by the illustrated secretion of Cl- into the lumen. Recall that water always moves across membranes by osmosis. Once Cl- moves into the lumen, water follows by osmosis.
The movement of Cl- across the apical membrane occurs via a Cl- channel. This channel is unusual in two ways. First, it is an ABC cassette protein. Second it is opened by phosphorylation. The activation of the kinase that phosphorylates this channel occurs via both normal physiological factors and by toxins released by certain strains of E. coli and other bacteria. Traveller's diarrhea is often due to strains of E. coli that release such toxins.
Refer again to the figure. The Cl- concentration is kept high in the cell via the cotransporter for Cl-, Na+ and K+ in the basolateral membrane. The concentration of Na+ is always much greater in the extracellular fluid than inside the cell due to the Na+/K+ active transporter. The strong concentration gradient for Na+ ensures that the cotransporter moves Cl- from the extracellular fluid into the cell.
(Note: For simplicity, we have ignored that movements of ions lead to electrical potential differences. As a result, when either Na+ or Cl- alone cross a membrane, oppositely charged ions will follow to preserve electrical neutrality. This occurs, of course, but is not included in the figures so that the dominant factors are not obscured.)