Na⁺/Ca²⁺ exchanger contributes to stool transport in mice with experimental diarrhea

The Na⁺/Ca²⁺ exchanger (NCX) is a bidirectional transporter that is controlled by membrane potential and transmembrane gradients of Na⁺ and Ca²⁺. To reveal the functional role of NCX on gastrointestinal motility, we have previously used NCX1 and NCX2 heterozygote knockout mice (HET). We found that NCX1 and NCX2 play important roles in the motility of the gastric fundus, ileum and distal colon. Therefore, we believed that NCX1 and NCX2 play an important role in transport of intestinal contents. Here, we investigated the role of NCX in a mouse model of drug-induced diarrhea. The fecal consistencies in NCX1 HET and NCX2 HET were assessed using a diarrhea induced by magnesium sulfate, 5-hydroxytryptamine (5-HT) and prostaglandin E₂ (PGE₂). NCX2 HET, but not NCX1 HET, exacerbated magnesium sulfate-induced diarrhea by increasing watery fecals. Likewise, 5-HT-induced diarrheas were exacerbated in NCX2 HET, but not NCX1 HET. However, NCX1 HET and NCX2 HET demonstrated PGE₂ induced diarrhea similar to those of wild-type mice (WT). As well as the result of the distal colon shown previously, in the proximal and transverse colons of WT, the myenteric plexus layers and the longitudinal and circular muscle layers were strongly immunoreactive to NCX1 and NCX2. In this study, we demonstrate that NCX2 has important roles in development of diarrhea.