Specific localization of an inwardly rectifying K⁺ channel, Kir4.1, at the apical membrane of rat gastric parietal cells; its possible involvement in K⁺ recycling for the H⁺‐K⁺‐pump

Abstract

Hydrochloric acid (HCl) is produced in parietal cells of gastric epithelium by a H+‐K+ pump. Protons are secreted into the gastric lumen in exchange for K+ by the action of the H+‐K+‐ATPase. Luminal K+ is essential for the operation of the pump and is thought to be supplied by unidentified K+ channels localized at the apical membrane of parietal cells. In this study, we showed that histamine‐ and carbachol‐induced acid secretion from isolated parietal cells monitored by intracellular accumulation of aminopyrine was depressed by Ba2+, an inhibitor of inwardly rectifying K+ channels. Among members of the inwardly rectifying K+ channel family, we found with reverse transcriptase‐polymerase chain reaction analyses that Kir4.1, Kir4.2 and Kir7.1 were expressed in rat gastric mucosa. With immunohistochemical analyses, Kir4.1 was found to be expressed in gastric parietal cells and localized specifically at their apical membrane. The current flowing through Kir4.1 channel expressed in HEK293T cells was not affected by reduction of extracellular pH from 7.4 to 3. These results suggest that Kir4.1 may be involved in the K+ recycling pathway in the apical membrane which is required for activation of the H+‐K+ pump in gastric parietal cells.

Kir4.1 Channel Expression Is Essential for Parietal Cell Control of Acid Secretion

“…However, Fujita et al (12) found several members of the Kir family of inwardly rectifying K ϩ channels expressed in rat gastric mucosa, and this was confirmed by others (9,13,14). The only study in which PC tubulovesicular and secretory membranes were isolated, reconstituted in lipid bilayer, and studied electrophysiologically found channels with Kir rather than KCNQ1 channel properties (13).…”

“…When colocalization of Kir4.1 with the H ϩ /K ϩ -ATPase in the tubulovesicles as well as the stimulated secretory membranes had been observed (12)(13)(14), we and others believed that Kir4.1 channels may serve to bring K ϩ to the extracellular K ϩ -binding site of the H ϩ /K ϩ -ATPase during stimulation of acid secretion. In this scenario, the acid secretory rate should be decreased in Kir4.1 KO mucosa.…”

Evidence for the regulation of left-right asymmetry inCiona intestinalis by ion flux

“…In the contexts of LR asymmetry and mammalian gastric tissues, the Kir4.1 K ϩ channel is a required partner for the physiological activity of the H ϩ K ϩ ATPase (Fujita et al, 2002;Levin et al, 2002;Chen and Levin, 2004). Correspondingly, we conducted a preliminary screen to identify potential types of channels involved in regulating LR asymmetry in Ciona (Table 1).…”

A mutation in the zebrafish Na,K‐ATPase subunit atp1a1a.1 provides genetic evidence that the sodium potassium pump contributes to left‐right asymmetry downstream or in parallel to nodal flow

“…With respect to the basic physiology of the cell, H,K-ATPases contribute to the electrochemical potential mostly through establishing a proton gradient, as the H ϩ /K ϩ antiport is electrically neutral. However H,K-ATPases may act together with a K ϩ channel to result in a net loss of positive charges (Fujita et al, 2002 drives asymmetric Calcium concentrations and activation of Notch signaling during initiation of LR asymmetry. A model has been suggested in which an electrochemical gradient along the left-right axis drives asymmetric Calcium distribution to high levels of Ca 2ϩ on the left side, which in turn activates Notch signaling (Raya et al, 2003(Raya et al, , 2004.…”