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

doi:10.1113/jphysiol.2001.013439

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

Akikazu Fujita ‡, Yoshiyuki Horio §, Kayoko Higashi †, Tomoyoshi Mouri , Fumiaki Hata ‡, Noriaki Takeguchi ¶ and Yoshihisa Kurachi *

* Department of Pharmacology II and †Department of Otolaryngology, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871, ‡ Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Science, Osaka Prefecture University, 1-1 Gakuenchou, Sakai, Osaka 599-8531, § Department of Pharmacology, Sapporo Medical University School of Medicine, South 1, West 17, Chuo-ku, Sapporo 060-8556 and ¶ Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan

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.

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