Background and aim: 

K⁺ recycling across the parietal cell (PC) apical membrane is essential for gastric acid secretion, and both Kir4.1 and KCNQ1 K⁺ channels have been recently found to traffic to the apical membrane during acid stimulation. This study was undertaken to explore the functional role of KCNQ1 and Kir4.1 channels in gastric acid secretion.

Results: 

Forskolin-stimulated acid secetrory rates were strongly reduced in KCNQ1-/- gastric mucosa of 7 day-old mice in mini-Ussing chamber setups. Application of a high K⁺ concentration to the luminal membrane restored normal acid secretory rates in the KNCQ1-/-mucosa, indicating that the primary function of KCNQ1 is the supply of K⁺ to the extracellular K⁺ binding site of the H⁺/K⁺-ATPase. Surprisingly, Kir4.1-/- mucosa secreted significantly more acid and initiated secretion more rapidly. Electrone microscopy revealed the presence of fully elaborate but collapsed canalicular membranes and a lack of tubulovesicles in resting state Kir4.1-/- parietal cells. After in vitro stimulation by forskolin, massive membrane fusion and canalicular enlargment was seen in the WT but not in the Kir4.1-/- mucosae, suggesting that Kir4.1 is essential for the membrane recycling events that accompany the acid secretory cycle. Parietal cell numbers were equal between wt and both KNCQ1- and Kir4.1-deficient gastric mucosae, but in Kir4.1-/- mucusae, H⁺/K⁺ ATPase mRNA was increased while that for AE2 mRNA, the basolateral anion exchanger which is highly expressed in parietal cells and therefore are excellent marker for parietal cell abundance, was normal.

Conclusions: 

KCNQ1 channels are the major pathway to provide K⁺ as substrate for H⁺/K⁺ ATPase. Kir4.1 channels are involved in the control of tubolovesicular fusion and/or retrieval.