Segmental variability of membrane conductances in rat and human colonic epithelia

Abstract

The membrane conductances in proximal and distal segments of rat and human colon were studied with microelectrodes, nystatin, ion channel blockers and Cl replacement. The results reveal that (1) in rat colon, total conductance (Gt) is greater in the proximal segment than in the distal segment, reflecting greater values of apical (Ga) and paracellular shunt (Gs) conductances in the proximal segment; in contrast, in human colon, Gt and its individual membrane components are similar in the proximal and distal segments, and lower than the corresponding values in rat colon; (2) amiloride sensitive apical Na conductances are absent in rat proximal colon, rat distal colon, and human proximal colon, but in human distal colon amiloride produces changes consistent with blockade of an apical Na conductance and inhibition of electrogenic Na transport; (3) a TEA-sensitive apical K conductance may be present in rat proximal colon (a K secretory epithelium), but not in rat distal colon (a K absorptive epithelium) or in either segment of human colon; and (4) in rat colon, replacement of mucosal and serosal Cl produces changes consistent with a substantial paracellular shunt permeability to Cl which is more marked in the proximal segment, whereas in human colon Cl replacement results in changes which suggest a relatively small paracellular shunt permeability to Cl which is similar in both segments. These data indicate marked segmental differences in Na, K and Cl transport in rat and human colon, and emphasise the hazards of applying models of colonic electrolyte transport in one species to another.

Sodium transport across the caecal and colonic epithelium of germfree and specific-pathogen free rats

“…In other experiments with normally fed rats, no indications of sodium channels in the distal colon were observed (Sandle and McGlone, 1987;Rajendran et al, 1989). After an incubation of the rat 'colon descendence' for 7 h with dexamethasone, the level of electroneutral sodium absorption in the proximal section was enhanced, and in the distal section electrogenic sodium absorption was seen (Bridges et al, 1987).…”

Fluid and Electrolyte Transport in Human Colon in Health and Disease

“…It is important to note that reported basal values of transepithelial pd, short-circuit current (Isc) , and ion fluxes (particularly those of sodium) vary widely between different in vitro studies. These variations probably reflect factors such as pre-operative sodium balance, type of pre-operative bowel preparation, the degree of tissue hypoxia during colonic resection, and the speed with which mucosal specimens are mounted in chambers and bathed in oxygenated electrolyte solutions (Grady et al 1970), rather than the segment of colon resected (Hubel et al 1987;Sandie and McGlone 1987;Sellin and De Soignie 1987;SandIe 1989) or the degree of handling of the specimen prior to mounting in the chamber (Grady et al 1970). …”

Basolateral potassium (IKCa) channel inhibition prevents increased colonic permeability induced by chemical hypoxia

“…We obtained sigmoid colon from patients undergoing resection for colonic cancer after first obtaining their informed, written consent. Segments of tissue 10 cm in length were taken at least 10 cm from the cancer, and sheets of mucosa stripped of their underlying serosa and muscle were prepared as described previously (30). Each mucosal sheet was divided into two equal parts and mounted in paired Ussing chambers.…”

“…Tissues (area 0.5 cm 2 ) were bathed on the mucosal side with a solution containing (in mM) 114 K ϩ gluconate, 25 KHCO3, 1.2 KH2PO4, 10 Ca 2ϩ methane sulfonate, 1.2 MgSO 4, and 11 glucose, and on the serosal side with a solution containing 113 Na ϩ gluconate, 25 NaHCO3, 5.8 K ϩ gluconate, 1.2 KH2PO4, 10 Ca 2ϩ methane sulfonate, 1.2 MgSO4, and 11 glucose. Both solutions were gassed with 95% O 2 and 5% CO2 and maintained at 37°C (30). Under open-circuit conditions, transepithelial voltage (VT) was monitored with KC1-4% agar bridges, and Ag-AgCl electrodes placed at opposite ends of the chamber were used to pass 2.5-s rectangular current pulses (I; ϭ 50 A) across the tissue.…”