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 Ca(2+) -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.