Figure 7. Cellular model of aldosterone-regulated electrogenic K⁺ secretion in the distal colon.

Normal distal colon secretes both K⁺ and Cl⁻ across the apical membrane. Na⁺, K⁺ ATPase (~) activity drives overall transport by establishing the Na⁺ gradient that allows basolateral uptake of K⁺ and Cl⁻ via NKCC1. Apical membrane secretion of K⁺ and Cl⁻ is supported by basolateral exit of Cl⁻ and K⁺ ions, respectively, to maintain the necessary electrochemical gradient. Multiple basolateral K⁺ and Cl⁻ channels may be involved in this process, including intermediate conductance (IK) and voltage-gated (K_V7.1) K⁺ channels, as well as CLC-2 Cl⁻ channels. Aldosterone stimulates electrogenic K⁺ secretion by increasing basolateral Na⁺, K⁺ ATPase activity (represented by enlarged arrows) and increasing the expression and activity of BK channels and NKCC1 co-transporter (represented by enlarged image objects and arrows, respectively). Electrogenic K⁺ secretion is inhibited by either IbTX (apical membrane BK channels) or bumetanide (basolateral NKCC1). To support the aldosterone-induced sustained K⁺ secretion at the apical membrane, basolateral Cl⁻ exit also must presumably be enhanced, although the identity of the channel(s) involved remains undetermined. Despite the increase in NKCC1 expression and activity, electrogenic Cl⁻ secretion is not enhanced by aldosterone, suggesting that the regulation of NKCC1 by aldosterone is specific to the K⁺ transport pathway.