Electrogenic ion transport in mammalian colon involves an ammonia-sensitive apical membrane K+ conductance

It is remarkable that high ammonia concentrations can be present within the colonic lumen without compromising normal epithelial function. We investigated the impact of luminal ammonia on Cl- secretion in native tissue. Stripped human colonic mucosa and unstripped rat distal colon were used. Paired samples were mounted in modified Ussing chambers for electrophysiological studies. In rat distal colon, apical ammonia dose-dependently blocked forskolin-activated short-circuit current with an IC50 to approximately 5 mM. Basolateral NH4Cl was less effective. Luminal methylamine (50 mM), chromanol 293B (10-50 microM), and Ba2+ (5 mM) blocked cAMP-activated short-circuit current but apical clotrimazole (100 microM) was without effect. In stripped human colonic mucosa, luminal but not basolateral NH4Cl (10 mM) and luminal Ba2+ (5 mM) suppressed forskolin-activated short-circuit current. Ammonia may be an endogenous regulator of colonic water and salt secretion. Apical K+ channels may be involved in the regulation of cAMP-stimulated Cl- secretion in mammalian colon.