Figure 2.

Integrated model of active Ca²⁺ reabsorption in the intestine and distal part of the nephron. Apical entry of Ca²⁺ is facilitated by Transient Receptor Potential Cation Channel Subfamily V Members 5,6 (TRPV 5,6)/Epithelial calcium channel (EcaC); Ca²⁺ then binds to calbindin-D_28K, and this complex diffuses through the cytosol to the basolateral membrane, where Ca²⁺ is extruded by a Na⁺/Ca²⁺ exchanger and a plasma membrane Ca²⁺-ATPase. The individually controlled steps in the activation process of the rate-limiting Ca²⁺ entry channel include 1α,25(OH)₂D₃-mediated transcriptional and translational activation, shuttling to the apical membrane, and subsequent activation of apically located channels by ambient Ca²⁺ concentration, direct phosphorylation, and/or accessory proteins. (Modified from Kumar and Vallon; Ref. 112.)