Skin electrodes are the most convenient reference electrodes for clinical measurements of electrical potential differences (pd) across the epithelium of the alimentary tract but the presence of an electrical charge on normal skin introduces an error. In the present study, by comparison with results obtained using subcutaneous and intravenous electrodes, it was shown that an intradermal injection of saline abolished the skin potential differences. This simple method, therefore, allows skin electrodes to be used to measure the true transepithelial potential differences of gut mucosa. The method was applied to investigate the effect on the rectal potential difference of altering the composition of the luminal solutions. Changes in the cations (sodium, potassium, magnesium) showed that sodium was the most important cationic determinant of the potential difference, especially when sodium absorption was stimulated by giving mineralocorticoids. Changes in the anions (chloride, iodide, bromide, nitrate, bicarbonate, sulphate, phosphate, citrate, and acetate) indicated that the molecular size of the anion rather than its chemical nature was the significant factor and suggested that the ions had to cross a barrier relatively impermeable to anions of radius greater than 3·5 to 4 A°. Changes in osmolality and glucose concentration were without effect.
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