The effect of claudin-15 deletion on cationic selectivity and transport of paracellular pathways in the cecum and large intestine

Abstract

The large intestine plays a pivotal role in water and electrolyte balance. It is thought that paracellular transport plays a role in water and ion transport mechanisms in the cecum and large intestine, however, these mechanisms and the physiological roles have rarely been studied. Claudin-15 forms a Na+ channel in tight junctions in the small intestine but its role in the cecum and colon has not been investigated. This study aimed to explore physiological roles of claudin-15 in the mouse cecum and colon using claudin-15 (Cldn15) KO mice. Transmural electrical conductance, current, flux of Na+, and dilution potential were assessed in isolated preparations of cecum and colon from Cldn15 KO mice mounted in Ussing chambers. The induced current of short-chain fatty acids, which are fermentative products in the cecum and colon, was also measured. In the cecum but not the middle large intestine, electrical conductance and paracellular Na+ flux were decreased, while in both the cecum and the colon, paracellular Na+ permeability was decreased in Cldn15 KO mice. These results suggest that claudin-15 is the molecule responsible for cation selectivity in tight junctions of the cecum and colon, and decreased cation selectivity in the cecum may cause impaired absorption function.