Colonic Potassium Absorption and Secretion in Health and Disease.

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- (HKCα ) and β- (HKCβ ) subunits which, when coexpressed, exhibit ouabain-insensitive H+ ,K+ -ATPase activity in HEK293 cells, while HKCα coexpressed with the gastric β-subunit exhibits ouabain-sensitive H+ ,K+ -ATPase activity in Xenopus oocytes. Aldosterone enhances apical H+ ,K+ -ATPase activity, HKCα 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.