Colonic Potassium Absorption and Secretion in Health and Disease

Abstract

The colon has large capacities for K⁺ absorption and K⁺ secretion, but its role in maintaining K⁺ homeostasis is often overlooked. For many years, passive diffusion and/or solvent drag were thought to be the primary mechanisms for K⁺ absorption in human and animal colon. However, it is now clear that apical H⁺ ,K⁺ -ATPase, in coordination with basolateral K⁺ -Cl^- cotransport and/or K⁺ and Cl^- channels operating in parallel, mediate electroneutral K⁺ absorption in animal colon. We now know that K⁺ absorption in rat colon reflects ouabain-sensitive and ouabain-insensitive apical H⁺ ,K⁺ -ATPase activities. Ouabain-insensitive and ouabain-sensitive H⁺ ,K⁺ -ATPases are localized in surface and crypt cells, respectively. Colonic H⁺ ,K⁺ -ATPase consists of α- (HKC_α ) and β- (HKC_β ) subunits which, when coexpressed, exhibit ouabain-insensitive H⁺ ,K⁺ -ATPase activity in HEK293 cells, while HKC_α coexpressed with the gastric β-subunit exhibits ouabain-sensitive H⁺ ,K⁺ -ATPase activity in Xenopus oocytes. Aldosterone enhances apical H⁺ ,K⁺ -ATPase activity, HKC_α specific mRNA and protein expression, and K⁺ absorption. Active K⁺ secretion, on the other hand, is mediated by apical K⁺ channels operating in a coordinated way with the basolateral Na⁺ -K⁺ -2Cl^- cotransporter. Both Ca²⁺ -activated intermediate conductance K⁺ (IK) and large conductance K⁺ (BK) channels are located in the apical membrane of colonic epithelia. IK channel-mediated K⁺ efflux provides the driving force for Cl^- secretion, while BK channels mediate active (e.g., cAMP-activated) K⁺ secretion. BK channel expression and activity are increased in patients with end-stage renal disease and ulcerative colitis. This review summarizes the role of apical H⁺ ,K⁺ -ATPase in K⁺ absorption, and apical BK channel function in K⁺ secretion in health and disease. © 2018 American Physiological Society. Compr Physiol 8:1513-1536, 2018.