Bicarbonate ion transport by the electrogenic Na + /HCO 3 - cotransporter, NBCe1, is required for normal electrical slow-wave activity in mouse small intestine

Normal gastrointestinal motility depends on electrical slow-wave activity generated by interstitial cells of Cajal (ICC) in the tunica muscularis of the gastrointestinal tract. A requirement for HCO in extracellular solutions used to record slow waves indicates a role for HCO transport in ICC pacemaking. The Slc4a4 gene transcript encoding the electrogenic Na /HCO cotransporter, NBCe1, is enriched in mouse small intestinal myenteric region ICC (ICC-MY) that generate slow waves. This study aimed to determine how extracellular HCO concentrations affect electrical activity in mouse small intestine and to determine the contribution of NBCe1 activity to these effects. Immunohistochemistry and sharp electrode electrical recordings were used. The NBCe1 immunoreactivity was localized to ICC-MY of the tunica muscularis. In sharp electrode electrical recordings, removal of HCO from extracellular solutions caused significant, reversible, depolarization of the smooth muscle and a reduction in slow-wave amplitude and frequency. In 100 mM HCO , the muscle hyperpolarized and slow wave amplitude and frequency increased. The effects of replacing extracellular Na with Li , an ion that does not support NBCe1 activity, were similar to, but larger than, the effects of removing HCO . There were no additional changes to electrical activity when HCO was removed from Li containing solutions. The Na /HCO cotransport inhibitor, S-0859 (30µM) significantly reduced the effect of removing HCO on electrical activity. These studies demonstrate a major role for Na /HCO cotransport by NBCe1 in electrical activity of mouse small intestine and indicated that regulation of intracellular acid:base homeostasis contributes to generation of normal pacemaker activity in the gastrointestinal tract.