Background: 

K⁺ recycling over the apical membrane is essential for gastric acid secretion, and both Kir 4.1 and KCNQ1 K⁺ channels have been recently found to traffic to the parietal cell apical membrane during acid stimulation.

Aims: 

To understand the physiological role of these channels by studying the acid secretory capacity and parietal cell morphology of very young Kir 4.1- and KNCQ1- deficient, heterozygotic and wildtype (WT) mice.

Methods and Results: 

At very young age (7–9 days), KCNQ1 -/- gastric mucosa in Ussing- chambers was able to secrete acid, but basal and forskolin-stimulated acid secretory rates were strongly reduced in KCNQ1-/- compared with +/+ and +/­ mice, whereas the Isc response, indicative of electrogenic anion secretion, was significantly increased. Electron micrographs displayed similar PC cell numbers in +/+ and -/- stomach, but hyperproduction of tubulovesicles and secretory membranes, as well as membrane filled autophagosomes in KCNQ1-/- parietal cells. Surprisingly, Kir 4.1 -/- mucosa secreted significantly more (24 %), and, more importantly, much faster (238 % of control increase after 10 min) acid, with a significant overshoot upon forskolin-stimulation compared to +/+ and +/­ mucosa, despite the fact that the Kir 4.1 -/- mice were smaller and the gastric mucosa thinner than the WT mice.

Conclusions: 

KCNQ1 channels are crucial for gastric acid secretion at a very young age by regulating K⁺ recycling and maintaining the viability of tubulovesicles and canaliculi in parietal cells. Kir 4.1 channels have a distinctly different function, seemingly acting as a "brake" on initial proton pumping and thus ATP consumption.