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‐ (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.