Although many factors can influence intracellular pH (pHi), some of the most important are those that involve the movement of acids and bases across the cell membrane. We will discuss recent results concerning barriers to the movement of H+, NH3 and CO2 across the apical cell membranes of gastric gland cells. Cell membranes are generally highly permeable to small, lipophilic molecules such as NH3 and CO2. In fact, only two examples are known of membranes relatively impermeable to NH3 and none membranes permeable to CO2. We recently developed a technique for perfusing the lumen of a single hand-dissected gastric gland on the stage of a microscope, while monitoring pHi with a fluorescent dye. We observed the expected pHi changes when we exposed the basolateral (i.e. blood-side) membrane to a pH 6.4 solution (a large, rapid pHi decrease), to a pH 7.4 solution containing approximately 0.3 mmoll-1 NH3 (a large and rapid pHi increase) or to a pH7.4 solution equilibrated with 1% CO2 (a rapid pHi decrease of -0.08). However, pHi was not significantly affected by perfusing the lumen with a pH 1.4 solution, with a pH 7.4 solution containing as much as 2.7 mmoll-1 NH3 or with a pH 6.1 solution equilibrated with 100% CO2. These data indicate that a barrier at or near the apical membrane has a uniquely low permeability to H+, NH3 and CO2.

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