Tobey NA, Argote CM, Vanegas XC, Barlow W, Orlando RC. Electrical parameters and ion species for active transport in human esophageal stratified squamous epithelium and Barrett's specialized columnar epithelium. Am J Physiol Gastrointest Liver Physiol 293: G264-G270, 2007. First published April 12, 2007; doi:10.1152/ajpgi.00047.2007.-The human esophagus is lined by stratified squamous epithelium (ESSE), and in some subjects with reflux disease the distal esophagus becomes lined by Barrett's specialized columnar epithelium (BSCE). ESSE and BSCE differ both histologically and functionally, the latter evident by differences in their in vivo transmural electrical potential difference (PD), ESSE averaging Ϫ15 mV and BSCE being greater than Ϫ25 mV. In this report we examine the basis for this difference in PD. This is done by mounting endoscopic biopsies of ESSE from 25 subjects without esophageal disease and BSCE from 19 with Barrett's esophagus in mini-Ussing chambers for electrical recordings basally and after bathing solution ion replacement. The results show that the PD of human ESSE reflects a low level of active ion transport (5.1 Ϯ 0.8 A/cm 2 ) combined with a high level of tissue (electrical) resistance (344 Ϯ 34 ⍀ ⅐ cm 2 ) and that of BSCE reflects a high level of active transport (43.6 Ϯ 11.6 A/cm 2 ) combined with a low level of resistance (69 Ϯ 8 ⍀ ⅐ cm 2 ). Furthermore, active transport in ESSE was principally due to sodium absorption whereas in BSCE it was equally divided between sodium absorption and anion (chloride/ bicarbonate) secretion, the latter through an apical membrane, 4-acetamido4Ј-isothiocyano-2,2Ј-stilbenedisulfonic acid-sensitive anion channel. As an anion-secreting tissue with bicarbonate secretory capacity more than fivefold greater than ESSE, BSCE is better suited than ESSE for defense of the esophagus against reflux disease. mini-Ussing chambers; ouabain; potential difference; short-circuit current; electrical resistance; gastroesophageal reflux disease; ethoxyzolamide; 4-acetamido4Ј-isothiocyano-2,2Ј-stilbenedisulfonic acid THE HUMAN ESOPHAGUS IS LINED by stratified squamous epithelium (ESSE), and in ϳ10% of subjects with gastroesophageal reflux disease the ESSE of distal esophagus is destroyed and replaced to a varying extent by a lining of Barrett's specialized columnar epithelium (BSCE) (19). ESSE and BSCE differ not only structurally, as the names imply, but also functionally, and one marker of this functional difference is reflected by differences in their in vivo transmural electrical potential difference (PD). The in vivo PD for ESSE averages Ϫ15 Ϯ 5 mV and the in vivo PD for BSCE is typically greater than Ϫ25 mV (11,22,24,30,39). Since the PD, according to Ohm's law, is the product of current times (electrical) resistance, such differences in PD for ESSE and BSCE indicate that these epithelia have fundamental differences in ion transport and/or barrier properties. The nature of these differences, however, remains elusive, principally because of limitations in electrical reco...