Potassium Channelopathies and Gastrointestinal Ulceration

Abstract

Potassium channels and transporters maintain potassium homeostasis and play significant roles in several different biological actions via potassium ion regulation. In previous decades, the key revelations that potassium channels and transporters are involved in the production of gastric acid and the regulation of secretion in the stomach have been recognized. Drugs used to treat peptic ulceration are often potassium transporter inhibitors. It has also been reported that potassium channels are involved in ulcerative colitis. Direct toxicity to the intestines from nonsteroidal anti-inflammatory drugs has been associated with altered potassium channel activities. Several reports have indicated that the long-term use of the antianginal drug Nicorandil, an adenosine triphosphate-sensitive potassium channel opener, increases the chances of ulceration and perforation from the oral to anal regions throughout the gastrointestinal (GI) tract. Several of these drug features provide further insights into the role of potassium channels in the occurrence of ulceration in the GI tract. The purpose of this review is to investigate whether potassium channelopathies are involved in the mechanisms responsible for ulceration that occurs throughout the GI tract.

Keywords: Gastrointestinal tract; H⁺/K⁺-ATPase; Potassium channels; Ulceration.

Fig. 1

Gastric acid secretion and K⁺ channels in a parietal cell of the stomach. Acid is produced from the hydration of CO₂ to form H⁺ and HCO₃⁻. Apical and tubulovesicular K⁺ channels provide K⁺ recycling, which is required for the function of the proton pump, H⁺/K⁺-ATPase.

Fig. 2

K⁺ absorption and secretion in an epithelial cell of the distal colon. K⁺ absorption is mediated by an apical colonic H⁺/K⁺-ATPase followed by basolateral K⁺ channels. K⁺ secretion is mediated by the basolateral Na⁺/K⁺-ATPase and Na⁺/K⁺/2Cl⁻ cotransporter (NKCC1) followed by the efflux of apical K⁺ channels.