Warren S. Rehm

A model to explain uphill water transport in the mammalian stomach.

Under most conditions the osmotic gradient hypothesis can account for water movement in the stomach. However, in the resting in vivo dog stomach, with isotonic HCl bathing the mucosal surface, H + disappears and Na + appears at approximately the same rate and water moves from the blood to the mucosal bathing fluid, resulting in the production of a hypotonic fluid. In the present paper we have developed a conceptual model to explain these findings. According to the model the cells on the surface and those lining the pits are impermeable to both water and solutes, the site of the H + -Na + exchange is the tubules, and the tubules are permeable to water. In demonstrating how the model works we have first obtained expressions for the concentration profiles of the ions in the pits under conditions of no water flow and show that the fluid at the bottom of the pits would be hypertonic. We then allow the tubules to become permeable to water, with the result that water moves from blood to lumen while the number of osmotically active particles does not change (the loss of H + equals the gain of Na + ). We obtain an approximate quantitative picture during water flow by making the assumption that HCl and NaCl diffuse independently.

An analysis of the short-circuiting technique applied to in vivo tissues

Abstract This paper deals with the short-circuiting technique (SCT) in tissues with intact blood flow. Central to the analysis is the effect of a passive barrier of appreciable resistance in series with a membrane possessing an active ionic transport mechanism. With the SCT applied to the total system the p.d. across the active membrane may not be reduced to zero. In absence of bulk flow the concentration of ions within the system will change so that in the steady state the electrochemical gradients for passive ions will be zero. With blood flow the electrochemical gradients for passive ions within the system may not be reduced to zero, hence in the steady state passive ions may be transported. If an in vivo tissue consists of a flat cell layer in series with a passive barrier the SCT is applicable provided certain criteria are satisfied. For tissues that are not flat cell layers, such as the dog gastric mucosa and in which a distributed parameter circuit is needed to adequately represent them the SCT under in vivo conditions is not applicable in the sense of the Ussing-Zerahn concept. The current needed to reduce the p.d. across the in vivo gastric mucosa to zero may be substantially less than the true short-circuit current (the total current that would be required to reduce the p.d. across each cell to zero).

Unstirred-layer model for the long time-constant transient voltage response to current in epithelial tissue☆

Abstract In previous work on the in vitro frog gastric mucosa it was found that step currents produced a transmucosal voltage response of about 100 seconds duration. The voltage response can be formally represented by five resistors in series, with four of the resistors shunted by dielectric capacitors. It was shown that the two resistance-capacitor subcircuits with the longest time constants demand capacitors of the order of Farads cm−2 and that this portion of the transient can be explained on the basis of mechanisms involving the polarization of e.m.f.s. In the present paper a conceptual unstirred-layer model is presented in which the transient voltage response to step currents is comparable to the observed response in the gastric mucosa. In both the model and in the gastric mucosa the voltage response for small currents is linear and bilateral and deviates from linear bilateral behavior at higher current densities. The implication of the unstirred-layer model is discussed in relation to other models previously proposed as explanations for the long-time constant transient.

Ion Transport and Short-Circuit Technique

Publisher Summary This chapter discusses the use of the well known short-circuit technique for studying active and passive ion transport. This technique has been used primarily for deciding between passive and active ion transport and for the determination of the effect of agents and procedures on the rate of active ion transport of the type, in which the net active transport can be equated to the net transport of charge. Many workers seem to assume that, during short-circuiting, the membrane possessing the active transport mechanism is short-circuited. Most of the workers in this field use the simple Ussing-Zerahn equivalent circuit and imply that, it is adequate to represent complex tissues. It is generally accepted that if the transport of an ion is essentially zero under short-circuit conditions, then the conclusion is warranted that the ion in question is passive. There is also considerable misunderstanding among workers using the simple Ussing-Zerahn circuit concerning the relationship between the conductance of this circuit and that of the actual tissue. The chapter describes that (1) if all the ion transports are exclusively via conductive pathways, the criteria for passive ion transport of the Ussing are valid for both single- and double-membrane models, but (2) if there are nonconductive pathways for ions that cannot be represented by an equivalent-circuit conductive pathway, then the accepted criteria for passive transport are not valid. The chapter discusses conductive pathways for all the ions involved, and the fallacy of using the criteria for systems in which there are nonconductive pathways.

Conductance of epithelial tissues with particular reference to the frog's cornea and gastric mucosa

Abstract This paper presents an overview of the problem of measuring the conductance of biological tissues by an analysis of the transient voltage response to step currents of constant magnitude. In general, the voltage response of tissues is characterized by a small step change in voltage followed by an exponential like rise. In the case of the gastric mucosa the voltage appears to level off after about 20 msec but this is only apparent; it actually continues to increase for about 100 sec. In the case of the frog cornea the voltage response levels off in about 1 sec. The response of the cornea with the endothelium removed is essentially similar to that of the intact cornea. The response of the cornea with the epithelium removed leaving the endothelium plus stroma behaves like an ohmic resistor with the usual sweep speeds in the msec range. The response of the above tissues are analyzed in light of the problem of determining the resistance of biological tissues.

Proton conductance of cell membranes

Abstract Several workers have suggested that cell membranes have a high proton conductance. Our interest in this concept arose from the possibility that the nutrient (submucosal-facing) membrane of the gastric mucosa may have a high proton or hydroxyl ion conductance which would play a role in the regulation of the acid-base balance of the cell. We found that wide changes in the H + concentration of the fluid bathing the nutrient side of the in vitro frog gastric mucosa did not result in significant changes in p.d. However, a maintained change of the H + concentration of the bathing fluid would be expected to produce only a temporary change in p.d. Since a diffusion barrier is present on the nutrient side the temporary change in p.d. might be masked. An analysis of this possibility was made on the basis of a conceptual model and as a result of the analysis it is concluded that the proton (and/or OH − ) conductance of the nutrient membrane of the frog gastric mucosa is not a significant fraction of its total conductance. The present status of the proton conductance hypothesis with respect to striated muscle and to the secretory membrane of the gastric mucosa is reviewed.

Diffusion resistance of endothelium and stroma of bullfrog cornea determined by potential response to K

Corneas of bullfrog (Rana catesbeiana) were mounted between lucite chambers. A four-electrode system was used and the potential difference (PD) and the electrical resistance were measured. In intact corneas, the PD averaged 25 mV (acqueous side positive) and the electrical resistance 1.5 kQ - cm2. perfusion of the aqueous side with high K+ solutions resulted in a marked decrease in PD and a drop in the electrical resistance. Scraping the epithelium (leaving the stroma plus endothelium) resulted in a drop of the PD to about zero and a decrease in electrical resistance to about 0.1 kQ - CM2 and a very small PD response to a marked elevation of the K+ concentration on the aqueous side. On the basis of the above, it is obvious that the large delta PD in intact corneas, due to elevation of the K+ concentration, must be due to K+ diffusing from the aqueous side across the endothelium and stroma and reaching the epithelium. The duration of the PD response is therefore a measure of the resistance to diffusion of the stroma plus endothelium. A quantitiative analysis shows that under in vitro conditions the resistance of the endothelium plus stroma to the diffusion of ions is very low.

Electrolyte Content of the Corneal Stroma of the Bullfrog

Summary The Na+, K+, and Cl- content of aqueous humor of the bullfrog is 100, 2.4, and 82 meq/kg of water, respectively. The [Na+] and [K+] of the corneal stroma are significantly higher than those of the aqueous humor while the Cl- content of the stroma is essentially the same as that of the aqueous humor.

Ion and Water Transport in Gastric Mucosa

This chapter is limited to a review of some of the aspects of the basic mechanisms of ion and H20 transport. A detailed review of the whole area of the basic mechanisms of gastric HC1 production would make this text far too long. We will therefore be somewhat dogmatic in presenting conclusions, particularly for those aspects which have been covered in detail in recent reviews.(1–7) The latter have focused primarily on the problem of H+ and Cl− secretion, and have given relatively little attention to the important problem of the mechanism of water transport. Consequently we believe it is appropriate to devote an appreciable portion of this chapter to the problem of water transport.

Ion Transport in Gastric Mucosa

Publisher Summary This chapter focuses on ion transport in gastric mucosa. The muscosal surface of the stomach has a large number of openings, which are the gastric pits that produce the gastric secretion. The physiology of secretion can be roughly divided into two parts: one concerned with the basic mechanism by which the cells elaborate the secretion and the second with the control mechanisms. Gastric secretion is controlled by both hormonal and reflex mechanisms. The taste or smell of food can cause the stomach to secrete under conditions where the food does not come in contact with the mucosa. Food in contact with the stomach stimulates the liberation of the hormone gastrin from the antrum into the blood stream. The gastrin in the blood reaches the stomach and stimulates the formation of gastric juice. When the pH of the stomach contents reaches about 2, further liberation of gastrin is inhibited, the acid acting as a negative feedback to gastrin secretion. The chapter discusses the anatomy and physiology of the stomach. Active transport of H+ and Cl− is also analyzed in the chapter.